Compounds and Methods for Preparing Substituted 3-(1-amino-2-methylpentane-3-yl)phenyl Compounds
AssigneeAMPAC Fine Chemicals LLC
InventorsBrian MORGAN, Olivier DAPREMONT, Patrick BERGET, Ali SULEMAN, William DUBAY, Jeffrey D. BUTLER
Life of this patent
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Abstract
Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds from an isomerically pure starting material are described. In particular, methods of preparing a 3-(1-(dimethylamino)-2-methylpentane-3-yl)phenol as a substantially optically pure (R,R) stereoisomer are described. Using a method of the present invention, only the (R,R) and (S,S) stereoisomers of the target compound are produced, increasing the yield and stereoselectivity of the desired (R,R) stereoisomer.
Claims17
1-7. (canceled)
A method of preparing a substantially optically pure (R,R) stereoisomer of a compound of formula (V):
- or a pharmaceutically acceptable salt thereof, the method comprising:
- (i) reacting a substantially pure E-isomer of a compound of formula (I):
- or a pharmaceutically acceptable salt thereof with one or more reducing agents, and optionally an alkylating agent, thereby obtaining the compound of formula (V) or the pharmaceutically acceptable salt thereof as a mixture of (R,R) and (S,S) stereoisomers that is substantially free of (R,S) and (S,R) stereoisomers;
- and
- (ii) separating the (R,R) stereoisomer from the (S,S) stereoisomer in the mixture, thereby
- obtaining the substantially optically pure stereoisomer of a compound of formula (V),
- wherein R1 represents a hydrogen or an aliphatic, aryl, or phenolic oxygen protecting group, R4 represents CN or CH2N(R5)2, and R5 represents a hydrogen or alkyl.
(canceled)
(canceled)
A method of preparing a substantially optically pure (R,R) stereoisomer of a compound of formula (VII):
- or a pharmaceutically acceptable salt thereof, the method comprising:
- reducing a substantially pure E-isomer of a compound of formula (I):
- or a pharmaceutically acceptable salt thereof, thereby obtaining a compound of formula (VI):
- or a pharmaceutically acceptable salt thereof as a mixture of (R,R) and (S,S) stereoisomers of the compound of formula (VI) that is substantially free of (R,S) and (S,R) stereoisomers of compound of formula (VI);
- (ii) separating the (R,R) stereoisomer from the (S,S) stereoisomer in the mixture, thereby obtaining a substantially optically pure (R,R) stereoisomer of the compound of formula (VI) or the pharmaceutically acceptable salt thereof;
- and
- (iii) reacting the substantially optically pure (R,R) stereoisomer of the compound of formula (VI) or the pharmaceutically acceptable salt thereof with a reducing agent, and optionally an alkylating agent, thereby obtaining the substantially optically pure (R,R) stereoisomer of compound of formula (VII) or the pharmaceutically acceptable salt thereof,
- wherein R1 represents a hydrogen or an aliphatic, aryl, or phenolic oxygen protecting group, and R5 represents a hydrogen or alkyl.
A method of preparing a substantially optically pure (R,R) stereoisomer of a compound of formula (VII):
- or a pharmaceutically acceptable salt thereof, the method comprising:
- (i) reacting a substantially pure E-isomer of a compound of formula (I):
- or a pharmaceutically acceptable salt thereof with a reducing agent, and optionally an alkylating agent, thereby obtaining a compound of formula (IV):
- or a pharmaceutically acceptable salt thereof;
- (ii) reducing the compound of formula (IV) or the pharmaceutically acceptable salt thereof, thereby obtaining the compound of formula (VII) or the pharmaceutically acceptable salt thereof in a mixture of (R,R) and (S,S) stereoisomers that is substantially free of (R,S) and (S,R) stereoisomers;
- and
- (iii) separating the (R,R) and (S,S) stereoisomers in the mixture, thereby obtaining the substantially optically pure (R,R) stereoisomer of the compound of formula (VII) or a pharmaceutically acceptable salt thereof,
- wherein R1 represents a hydrogen or an aliphatic, aryl, or phenolic oxygen protecting group, and R5 represents a hydrogen or alkyl.
A method of preparing a substantially optically pure (R,R) stereoisomer of a compound of formula (VII):
- or a pharmaceutically acceptable salt thereof, the method comprising:
- (i) reacting a substantially pure E-isomer of a compound of formula (I):
- or a pharmaceutically acceptable salt thereof with one or more reducing agents, and optionally an alkylating agent, thereby obtaining a compound of formula (VII) or a pharmaceutically acceptable salt thereof in a mixture of (R,R) and (S,S) stereoisomers that is substantially free of (R,S) and (S,R) stereoisomers;
- and
- (ii) separating the (R,R) and (S,S) stereoisomers in the mixture, thereby obtaining the substantially optically pure (R,R) stereoisomer of the compound of formula (VII) or the pharmaceutically acceptable salt thereof,
- wherein R1 represents a hydrogen or an aliphatic, aryl, or phenolic oxygen protecting group, and R5 represents a hydrogen or alkyl.
23-24. (canceled)
Dependencies are inferred from the claim text.