Process for preparing cyclic CIS-1-amino-2-alkanols
AssigneeSepracor Inc.
InventorsYun Gao, Yaping Hong, Xiaoyi Nie, Roger P. Bakale, Richard R. Feinberg, Charles M. Zepp
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Abstract
A two-step process for the conversion of a trans-1-amino-2-hydroxycycloalkane stereoselectively to a cis-1-amino-2-hydroxycycloalkane is disclosed. The novel step, a one-step hydrolysis with formal inversion, can be used to convert an amide of a trans-1-amino-2-hydroxycycloalkane to a cis-1-amino-2-hydroxycycloalkane. Methods for obtaining the trans-1-amino-2-hydroxycycloalkanes and their amides from alkenes are also disclosed. A preferred process converts indene to cis-1-amino-2-indanol.
Claims24
A process for the stereospecific conversion of a trans-1-amino-2-hydroxycyclopentane to the corresponding cis-1-amino-2-hydroxycyclopentane comprising:
- (a) reacting said trans-1-amino-2-hydroxycyclopentane with an acylating agent to produce an amide;
- and
- (b) treating said amide with a solution of a strong acid to cleave the amide and effect inversion of the carbon bearing the hydroxyl function to produce a cis-1-amino-2-hydroxycyclopentane.
A process for the stereospecific conversion of an amide of a trans-1-amino-2-hydroxycyclopentane to the corresponding cis-1-amino-2-hydroxycyclopentane comprising treating said amide with a solution of a strong acid to cleave the amide and effect inversion of the carbon bearing the hydroxyl function to produce a cis-1-amino-2-hydroxycyclopentane.
A process for producing a cis-1-amino-2-indanol from an indene comprising the steps of:
- (a) oxidizing said indene to produce an indene oxide;
- (b) converting said indene oxide to an amide of a trans-1-amino-2-indanol;
- and
- (c) treating said amide of a trans-1-amino-2-indanol with a solution of a strong acid to cleave the amide and effect inversion of the carbon bearing the hydroxyl function to produce a cis-1-amino-2-indanol.
A process for producing a compound of formula ##STR13## comprising the steps of:
- (a) reacting a trans aminoalcohol of formula ##STR14## with an acylating agent of formula R.sup.4 CO-X to produce an amide of formula ##STR15## and (b) treating said amide with a solution of a strong acid, wherein
- R.sup.1 is hydrogen, alkyl, aryl or substituted aryl;
- R.sup.2 is hydrogen, alkyl, aryl or substituted aryl;
- R.sup.3 is hydrogen, alkyl, aryl or substituted aryl;
- R.sup.4 is hydrogen, alkyl, aryl or substituted aryl;
- R.sup.5 is hydrogen, alkyl, aryl or substituted aryl;
- or
- R.sup.1 and R.sup.2 together form a 1,2-fused alicyclic, aryl or substituted aryl residue;
- n is zero or an integer from one to three;
- and
- X is an activating group for the acylation of amines.
A process for the stereospecific conversion of a trans-1-amino-2-hydroxycyclohexane to the corresponding cis-1-amino-2-hydroxycyclohexane comprising:
- (a) reacting said trans-1-amino-2-hydroxycyclohexane with an acylating agent to produce an amide;
- and
- (b) treating said amide with an aqueous solution of a strong acid to cleave the amide and effect inversion of the carbon bearing the hydroxyl function to produce a cis-1-amino-2-hydroxycyclohexane.
A process for the stereospecific conversion of an amide of a trans-1-amino-2-hydroxycyclohexane to the corresponding cis-1-amino-2-hydroxycyclohexane comprising treating said amide with a solution of a strong acid to cleave the amide and effect inversion of the carbon bearing the hydroxyl function to produce a cis-1-amino-2-hydroxycyclohexane.
Dependencies are inferred from the claim text.