公开(公告)号：US3734952A

公开(公告)日：1973-05-22

申请号：US3734952D

申请日：1968-12-27

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A

IPC: C07C227/36 ,  A61K31/195 ,  C07C229/36 ,  C07D317/60 ,  E04C2/26 ,  E04C2/38 ,  C07C101/08

CPC classification number: A61K31/195 ,  C07D317/60 ,  E04C2/26 ,  E04C2/38

Abstract: THE PRESENT INVENTION RELATES TO A PROCESS FOR THE PREPARATION OF L-DOPA AND TO AN ARYL LOWER ALLKYLAMINE RESOLVING AGENT USABLE IN THIS PREPARATION.

公开(公告)号：US3832387A

公开(公告)日：1974-08-27

申请号：US23542172

申请日：1972-03-16

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07C205/53 ,  C07C79/46

CPC classification number: C07C205/53 ,  C07C201/10

Abstract: Alpha -nitro-cinnamic acid derivatives which are useful in preparing phenylalanines, and a process for obtaining the derivatives by treating the corresponding cinnamic acid esters with nitric oxide or nitrogen dioxide.

Abstract translation: 可用于制备苯丙氨酸的α-硝基肉桂酸衍生物，以及通过用一氧化氮或二氧化氮处理相应的肉桂酸酯来获得衍生物的方法。

公开(公告)号：US3716530A

公开(公告)日：1973-02-13

申请号：US3716530D

申请日：1971-08-10

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07J5/00 ,  C07J7/00 ,  C07J13/00 ,  C07C173/00 ,  C07C169/08

CPC classification number: C07J13/007 ,  C07J5/0053 ,  C07J7/0045

Abstract: A process for converting 17 Alpha -vinyl-17 Beta -hydroxy steroids to 17-(2-haloethylidene)-steroids, known intermediates for antifungal and progestational agents, by treating the 17 Alpha -vinyl-17 Beta -hydroxy steroids with vanadium tetrahalide.

Abstract translation: 通过用四卤化钒处理17α-乙烯基-17β-羟基类固醇，将17α-乙烯基-17β-羟基类固醇转化为17-（2-卤代亚乙基） - 类固醇，已知的抗真菌和促孕剂中间体的方法。

公开(公告)号：BR6680826D0

公开(公告)日：1973-12-26

申请号：BR18082666

申请日：1966-06-30

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07J5/00 ,  C07J7/00 ,  C07J75/00

Abstract: The invention comprises (1) a process for preparing 20-hydroxypregnanes, 19-nor-pregnanes and 10a -pregnanes by reacting a 17-keto steroid of the androstane, 10a -androstane or estrane series, in which any other keto groups are protected, with ethylidene-triphenylphosphorane to obtain a D 17(20)-pregnane, hydroborating this, and treating the product with hydrogen peroxide at a pH greater than 7 to obtain a 20-hydroxy-pregnane, followed if desired by one or more of (a) 20-esterification or oxidation; (b) regeneration of a protected keto group; (c) 3-etherification, esterification or oxidation; or (d) a Birch reduction, with optional isomerization of the product, (11) 3-hydroxy, C1- 7 alkoxy or C1- 7 alkanoyloxy-19-nor - pregna - 1,3,5(10), 17(20) - tetraenes, and (111) 3b -hydroxy, C1- 7 alkoxy, or tetrahydropyranyloxy, or 3,3 alkylene - 9b , 10a - pregn-17(20) enes. 3,3 - Ethylenedioxy - 5b , 9b , 10a - androstan-17b -ol is prepared by conversion of 5b ,9b ,10a -androstan - 17b - ol - 3 - one to its 3 - ethylene ketal, followed by oxidation with chromium trioxide. The 19-nor-pregna-1,3,5(10)-tetraenes of the invention have estrogenic activity and may be used in pharmaceutical compositions in combination with a carrier, for example in forms suitable for oral administration.

公开(公告)号：FI44907B

公开(公告)日：1971-11-01

申请号：FI173766

申请日：1966-06-29

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07J5/00 ,  C07J7/00 ,  C07J75/00 ,  C07C167/20

Abstract: The invention comprises (1) a process for preparing 20-hydroxypregnanes, 19-nor-pregnanes and 10a -pregnanes by reacting a 17-keto steroid of the androstane, 10a -androstane or estrane series, in which any other keto groups are protected, with ethylidene-triphenylphosphorane to obtain a D 17(20)-pregnane, hydroborating this, and treating the product with hydrogen peroxide at a pH greater than 7 to obtain a 20-hydroxy-pregnane, followed if desired by one or more of (a) 20-esterification or oxidation; (b) regeneration of a protected keto group; (c) 3-etherification, esterification or oxidation; or (d) a Birch reduction, with optional isomerization of the product, (11) 3-hydroxy, C1- 7 alkoxy or C1- 7 alkanoyloxy-19-nor - pregna - 1,3,5(10), 17(20) - tetraenes, and (111) 3b -hydroxy, C1- 7 alkoxy, or tetrahydropyranyloxy, or 3,3 alkylene - 9b , 10a - pregn-17(20) enes. 3,3 - Ethylenedioxy - 5b , 9b , 10a - androstan-17b -ol is prepared by conversion of 5b ,9b ,10a -androstan - 17b - ol - 3 - one to its 3 - ethylene ketal, followed by oxidation with chromium trioxide. The 19-nor-pregna-1,3,5(10)-tetraenes of the invention have estrogenic activity and may be used in pharmaceutical compositions in combination with a carrier, for example in forms suitable for oral administration.

公开(公告)号：DK123866B

公开(公告)日：1972-08-14

申请号：DK112467

申请日：1967-03-03

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07D317/72 ,  H02B1/048 ,  C07C167/20

Abstract: Carbocyclic 17-ethylidene steroids or 17-ethylidene - des A - steroids are obtained in a process which comprises reacting a carbocyclic 17-oxo-steroid or 17-oxo-des A-steroid (in which all oxo groups other than the 17-oxo group are protected) with a phosphorus compound of the formula wherein each of the symbols R1 and R2 represent a C1-C5 alkyl or phenyl (C1-C5 alkyl) group or the symbols R1 and R2 together represent a tetramethylene, pentamethylene or 3-oxa-pentamethylene group and each of the symbols R3 and R4 represents a phenyl or substituted phenyl group or grouping of the formula Specified phosphorus compounds are ethylidenetris - (dimethylamino) - phosphorane, ethylidene - bis - (diethylamino) - phenyl - phosphorane, and ethylidene-diethylamino-diphenyl phosphorane. Any 17-oxo-steroid or 17 oxo-des A steroid may be employed irrespective of the stereoconfiguration of the rings therein. Phosphonium salts of the formula wherein R1, R2, R3 and R4 are as defined above and X is iodine are obtained by treating the appropriate NR1R2 - diphenyl-, bis - (NR1R2)-phenyl- or tris-(NR1R2)-phosphine with ethyliodide. Treatment of these salts with an acid binding agent yields the phosphoranes mentioned above.

公开(公告)号：BR6680827D0

公开(公告)日：1973-12-26

申请号：BR18082766

申请日：1966-06-30

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07D317/72

Abstract: The invention comprises (a) a process for preparing 3a b - methyl - 3b - (1 - hydroxy -ethyl)-benz[e] -indene derivatives, including hydrogenated derivatives thereof, by reaction of a 3-oxo-3a b -methyl-benz-[e]-indene derivative, in which any keto groups other than in the 3-position are protected, with ethylidene-triphenyl phosphorono, to form a 3-ethylidene benz-[e]-indene derivative, if desired splitting off any ketone-protecting groups present, reducing any such keto group to an hydroxy group and converting this into its C1- 7 alkyl or 2-tetrahydropyranyl ether, and treating the 3-ethylidene compound so obtained first with a source of hydroboron radicals and then, at a pH greater than 7, with hydrogen peroxide, and (b) 3-ethylidene-intermediates of formula wherein R1 is a hydrogen atom or a C1- 7 alkyl group and Z is a carbonyl group, a group wherein R3 is a C1- 7 alkylene group, or a group wherein R2 is a hydrogen atom or a C1- 7 alkyl or 2-tetrahydropyranyl group. The 3b -hydroxy-ethyl side-chain may be oxidized to a 3b -acetyl side-chain. 3a b ,6(a or b )-dimethyl-3-oxo-7,7-ethylenedioxy-5a (a or b )-9ab -9ba -perhydro-benz-[e]-indenes are prepared by ketalization of the corresponding 7-oxo-3-hydroxy-compounds to form the 3-hydroxy-7,7-ethylenedioxy derivatives, followed by oxidation with chromium trioxide. 3a b ,6b - dimethyl - 3b - hydroxy - 7 - oxo - 5ab , 9ab ,9ba -perhydrobenz-[e]-indene is prepared by catalytic hydrogenation of the corresponding 5a,6-dehydro-compound. Progesterone and 20-hydroxy-3-oxo-D 4-9b ,10a -pregnane are prepared by condensation of the corresponding des-A-5-oxo-steroid with methyl vinyl ketone.

公开(公告)号：SE350251B

公开(公告)日：1972-10-23

申请号：SE902466

申请日：1966-07-01

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07D317/72 ,  C07C35/22

Abstract: The invention comprises (a) a process for preparing 3a b - methyl - 3b - (1 - hydroxy -ethyl)-benz[e] -indene derivatives, including hydrogenated derivatives thereof, by reaction of a 3-oxo-3a b -methyl-benz-[e]-indene derivative, in which any keto groups other than in the 3-position are protected, with ethylidene-triphenyl phosphorono, to form a 3-ethylidene benz-[e]-indene derivative, if desired splitting off any ketone-protecting groups present, reducing any such keto group to an hydroxy group and converting this into its C1- 7 alkyl or 2-tetrahydropyranyl ether, and treating the 3-ethylidene compound so obtained first with a source of hydroboron radicals and then, at a pH greater than 7, with hydrogen peroxide, and (b) 3-ethylidene-intermediates of formula wherein R1 is a hydrogen atom or a C1- 7 alkyl group and Z is a carbonyl group, a group wherein R3 is a C1- 7 alkylene group, or a group wherein R2 is a hydrogen atom or a C1- 7 alkyl or 2-tetrahydropyranyl group. The 3b -hydroxy-ethyl side-chain may be oxidized to a 3b -acetyl side-chain. 3a b ,6(a or b )-dimethyl-3-oxo-7,7-ethylenedioxy-5a (a or b )-9ab -9ba -perhydro-benz-[e]-indenes are prepared by ketalization of the corresponding 7-oxo-3-hydroxy-compounds to form the 3-hydroxy-7,7-ethylenedioxy derivatives, followed by oxidation with chromium trioxide. 3a b ,6b - dimethyl - 3b - hydroxy - 7 - oxo - 5ab , 9ab ,9ba -perhydrobenz-[e]-indene is prepared by catalytic hydrogenation of the corresponding 5a,6-dehydro-compound. Progesterone and 20-hydroxy-3-oxo-D 4-9b ,10a -pregnane are prepared by condensation of the corresponding des-A-5-oxo-steroid with methyl vinyl ketone.

公开(公告)号：NO125274B

公开(公告)日：1972-08-14

申请号：NO16372766

申请日：1966-06-30

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07J5/00 ,  C07J7/00 ,  C07J75/00 ,  C07C167/20

Abstract: The invention comprises (1) a process for preparing 20-hydroxypregnanes, 19-nor-pregnanes and 10a -pregnanes by reacting a 17-keto steroid of the androstane, 10a -androstane or estrane series, in which any other keto groups are protected, with ethylidene-triphenylphosphorane to obtain a D 17(20)-pregnane, hydroborating this, and treating the product with hydrogen peroxide at a pH greater than 7 to obtain a 20-hydroxy-pregnane, followed if desired by one or more of (a) 20-esterification or oxidation; (b) regeneration of a protected keto group; (c) 3-etherification, esterification or oxidation; or (d) a Birch reduction, with optional isomerization of the product, (11) 3-hydroxy, C1- 7 alkoxy or C1- 7 alkanoyloxy-19-nor - pregna - 1,3,5(10), 17(20) - tetraenes, and (111) 3b -hydroxy, C1- 7 alkoxy, or tetrahydropyranyloxy, or 3,3 alkylene - 9b , 10a - pregn-17(20) enes. 3,3 - Ethylenedioxy - 5b , 9b , 10a - androstan-17b -ol is prepared by conversion of 5b ,9b ,10a -androstan - 17b - ol - 3 - one to its 3 - ethylene ketal, followed by oxidation with chromium trioxide. The 19-nor-pregna-1,3,5(10)-tetraenes of the invention have estrogenic activity and may be used in pharmaceutical compositions in combination with a carrier, for example in forms suitable for oral administration.

公开(公告)号：SE331095B

公开(公告)日：1970-12-14

申请号：SE293767

申请日：1967-03-03

Applicant: HOFFMANN LA ROCHE

Inventor： KRUBINER A ,  OLIVETO E

IPC: C07D317/72 ,  H02B1/048 ,  C07C167/20

Abstract: Carbocyclic 17-ethylidene steroids or 17-ethylidene - des A - steroids are obtained in a process which comprises reacting a carbocyclic 17-oxo-steroid or 17-oxo-des A-steroid (in which all oxo groups other than the 17-oxo group are protected) with a phosphorus compound of the formula wherein each of the symbols R1 and R2 represent a C1-C5 alkyl or phenyl (C1-C5 alkyl) group or the symbols R1 and R2 together represent a tetramethylene, pentamethylene or 3-oxa-pentamethylene group and each of the symbols R3 and R4 represents a phenyl or substituted phenyl group or grouping of the formula Specified phosphorus compounds are ethylidenetris - (dimethylamino) - phosphorane, ethylidene - bis - (diethylamino) - phenyl - phosphorane, and ethylidene-diethylamino-diphenyl phosphorane. Any 17-oxo-steroid or 17 oxo-des A steroid may be employed irrespective of the stereoconfiguration of the rings therein. Phosphonium salts of the formula wherein R1, R2, R3 and R4 are as defined above and X is iodine are obtained by treating the appropriate NR1R2 - diphenyl-, bis - (NR1R2)-phenyl- or tris-(NR1R2)-phosphine with ethyliodide. Treatment of these salts with an acid binding agent yields the phosphoranes mentioned above.