Claims
- 1. A process for the production of spirocycles of Formula I wherein the process results an alcohol having an enantiomeric efficiency of 98% or higher ##STR27## where R.sub.1 is selected from the group consisting of CO--C.sub.1-3 alkyl, cyano, carboxy, carboxy C.sub.1-6 alkyl ester, carboxamido, C.sub.1-6 alkyl sulfinyl, C.sub.1-6 alkyl sulfonyl, C.sub.1-6 methansulfamido and halogen; comprising the steps of:
- (1) adding the benzylic ketone to methylene chloride in a ratio of about 0.032 moles of the benzylic ketone to 300 mL of methylene chloride and stirring to produce a slurry;
- (2) adding 5% aqueous sodium bicarbonate at a ratio of about 163 mL for every 0.032 moles of the benzylic ketone to the slurry and maintaining the temperature at about 20.degree.-25.degree. C.;
- (3) Stirring the mixture of step (2) for about 60 minutes;
- (4) Allowing the mixture of step (3) to settle;
- (5) Separating the organic layer of step (3) and washing it with half saturated brine;
- (6) Concentrating the methylene chloride phase by atmospheric distillation to a final volume of approximately 90% of the initial volume of methylene chloride used in step (1);
- (7) Cooling the solution of step (6) to about -18.degree. C.;
- (8) Adding a molar amount of borane methyl sulfide equal to about 2.4 times the molar mount of benzylic ketone of step (1) and adding a molar amount of isopropanol equal to from 1 to 3 times the number of moles of the benzylic ketone added in step (1);
- (9) Adding oxazaborolidine.BH.sub.3 complex as a solid and stirring the reaction for about 25 minutes at about -18.degree. C.;
- (10) Gradually increasing the temperature to about 18.degree. C. over about 35 minutes;
- (11) Stirring for about 45 to 60 minutes until the reaction is complete;
- (12) Adding methanol and mixing at about 18.degree. C. for about 30 minutes;
- (13) Distilling off methyl sulfide, methylene chloride and trimethylborate, with heat;
- (14) Adding additional methanol and heating to 63.degree.-65.degree. C. for 35 minutes to decompose the amine borane complex;
- (15) Adding acetonitrile and vacuum distillating to remove the methanol;
- (16) Adding water to the acetonitrile solution and seeding with authenetic crystals of the compound of Formula II to begin crystallization; and
- (17) Collecting the crystals of Formula II by filtration.
- 2. The method of claim 1 wherein the benzylic ketone is the ##STR28## compound of Formula I which is reduced to the compound of Formula II.
CROSS REFERENCE
This is a continuation-in-part from U.S. patent application Ser. No. 08/075,196, which was filed on Jun. 10, 1993, now abandoned.
US Referenced Citations (2)
Non-Patent Literature Citations (1)
Entry |
Carey et al "A new system for catalytic evautio-selective reduction" Tetrahedron Lett 31 611-614 (1990). |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
75196 |
Jun 1993 |
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