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    PRODUCTION OF BISPHOSPHONATE AS INTERMEDIATE FOR PRODUCING BISPHOSPHINE OXIDE COMPOUND AND BISPHOSPHINE LIGAND
    1.
    发明专利
    PRODUCTION OF BISPHOSPHONATE AS INTERMEDIATE FOR PRODUCING BISPHOSPHINE OXIDE COMPOUND AND BISPHOSPHINE LIGAND 失效

    公开(公告)号：JPH11246576A

    公开(公告)日：1999-09-14

    申请号：JP36404498

    申请日：1998-12-22

    Applicant: HOFFMANN LA ROCHE

    Inventor： FORICHER JOSEPH ,  SCHMID RUDOLF

    IPC: B01J31/24 ,  C07B37/04 ,  C07B57/00 ,  C07F9/40 ,  C07F9/53 ,  C07F9/655 ,  C07F9/6553

    Abstract: PROBLEM TO BE SOLVED: To obtain the subject intermediate by forming a racemic compound by reacting a specific compound with a specific compound in an organic solvent at a low temperature, then resolving the same. SOLUTION: This method for producing a bisphosphonate consists of reacting, etc., a compound of formula I (R , R are each H, a 1-8C alkyl or the like; R is H, a 1-8C alkyl or the like; R is a 1-8C alkoxy or the like), with 0.5-3 equivalent, preferably 0.9-1.2 equivalent of a compound of formula II (R is a 1-8C alkyl, phenyl or the like; R is a 1-8C alkyl, a 3-6C cycloalkyl), etc., in an organic solvent at a temp. of (-)70-20 deg.C, preferably at a temp. of (-)30-0 deg.C, then adding 0.5-3 equivalent, preferably 1-1.5 equivalent of a metal salt (complex) having oxidizing capacity at a temp. of (-)70-20 deg.C, preferably at a temp. of (-)30-20 deg.C to obtain a racemic compound of formula III, etc., and if desired, performing a resolution of the racemic compound, and converting the obtained bisphosphonate to bisphosphine oxide.

    5.
    发明专利
    未知

    公开(公告)号：DE69807832T2

    公开(公告)日：2003-07-31

    申请号：DE69807832

    申请日：1998-12-17

    Applicant: HOFFMANN LA ROCHE

    Inventor： FORICHER JOSEPH ,  SCHMID RUDOLF

    IPC: B01J31/24 ,  C07B37/04 ,  C07B57/00 ,  C07F9/40 ,  C07F9/53 ,  C07F9/655 ,  C07F9/6553

    Abstract: A process for the manufacture of bisphosphine oxide compounds and bisphosphonates as intermediates for the production of bisphosphine ligands, in which in a single step process a) a phosphine oxide compound is reacted in an organic solvent at -70 DEG C to 20 DEG C with 0.5-3 eq. of a lithium or magnesium amide compound, b) 0.5-3 eq. of oxidatively-acting metal salt or metal salt complex are added to the mixture obtained in stage a) in a temperature range of -70 DEG C to 20 DEG C, with a racemate of a bisphosphine oxide compound being obtained; c) a racemate cleavage is carried out if desired; and d) the bisphosphonates obtained in stage b) or c) are converted into bisphosphine oxides.

    6.
    发明专利
    未知

    公开(公告)号：DK0530336T3

    公开(公告)日：1996-05-20

    申请号：DK92905551

    申请日：1992-03-11

    Applicant: HOFFMANN LA ROCHE

    Inventor： HEISER BERND ,  BROGER EMIL ALBIN ,  SCHMID RUDOLF ,  FORICHER JOSEPH

    IPC: B01J31/28 ,  C07B57/00 ,  C07C29/17 ,  C07F9/572 ,  C07F9/655 ,  C07F9/6553 ,  C07F15/00

    Abstract: PCT No. PCT/CH92/00049 Sec. 371 Date Nov. 13, 1992 Sec. 102(e) Date Nov. 13, 1992 PCT Filed Mar. 11, 1992 PCT Pub. No. WO92/16536 PCT Pub. Date Oct. 1, 1992.Novel, racemic and optically active phosphorus compounds of the formula I wherein R signifies lower alkyl, lower alkoxy or a protected hydroxy group, R1 signifies a five membered heteroaromatic ring, R2 stands for lower alkyl or lower alkoxy and n represents the number 0, 1 or 2, are described. The compounds of formula I serve in the form of complexes with a metal of Group VIII as catalyst for asymmetric hydrogenations and for enantioselective hydrogen displacements in prochiral allylic systems.

    8.
    发明专利
    未知

    公开(公告)号：DE69807832D1

    公开(公告)日：2002-10-17

    申请号：DE69807832

    申请日：1998-12-17

    Applicant: HOFFMANN LA ROCHE

    Inventor： FORICHER JOSEPH ,  SCHMID RUDOLF

    IPC: B01J31/24 ,  C07B37/04 ,  C07B57/00 ,  C07F9/40 ,  C07F9/53 ,  C07F9/655 ,  C07F9/6553

    Abstract: A process for the manufacture of bisphosphine oxide compounds and bisphosphonates as intermediates for the production of bisphosphine ligands, in which in a single step process a) a phosphine oxide compound is reacted in an organic solvent at -70 DEG C to 20 DEG C with 0.5-3 eq. of a lithium or magnesium amide compound, b) 0.5-3 eq. of oxidatively-acting metal salt or metal salt complex are added to the mixture obtained in stage a) in a temperature range of -70 DEG C to 20 DEG C, with a racemate of a bisphosphine oxide compound being obtained; c) a racemate cleavage is carried out if desired; and d) the bisphosphonates obtained in stage b) or c) are converted into bisphosphine oxides.

    9.
    发明专利
    未知

    公开(公告)号：AT223923T

    公开(公告)日：2002-09-15

    申请号：AT98123996

    申请日：1998-12-17

    Applicant: HOFFMANN LA ROCHE

    Inventor： FORICHER JOSEPH ,  SCHMID RUDOLF

    IPC: B01J31/24 ,  C07B37/04 ,  C07B57/00 ,  C07F9/40 ,  C07F9/53 ,  C07F9/655 ,  C07F9/6553

    Abstract: A process for the manufacture of bisphosphine oxide compounds and bisphosphonates as intermediates for the production of bisphosphine ligands, in which in a single step process a) a phosphine oxide compound is reacted in an organic solvent at -70 DEG C to 20 DEG C with 0.5-3 eq. of a lithium or magnesium amide compound, b) 0.5-3 eq. of oxidatively-acting metal salt or metal salt complex are added to the mixture obtained in stage a) in a temperature range of -70 DEG C to 20 DEG C, with a racemate of a bisphosphine oxide compound being obtained; c) a racemate cleavage is carried out if desired; and d) the bisphosphonates obtained in stage b) or c) are converted into bisphosphine oxides.

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