Lithium borohydride → 1,1-Dimethylethyl (2R,4S)-2-(hydroxymethyl)-4-methyl-1-pyrrolidinecarboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@@H:9]1[C:14](OC)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Li+]>>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@@H:9]1[CH2:14][OH:15])=[O:7])([CH3:3])([CH3:4])[CH3:2]Participants
Procedure
(2R,4S)-4-Methylpyrrolidine-2-carboxylic acid described in J. Chem. Soc. C, pp. 514-522 (1971) is reacted with di-tert-butyl dicarbonate to give (2R,4S)-1-tert-butoxycarbonyl-4-methylpyrrolidine-2-carboxylic acid. (2R,4S)-1-tert-Butoxycarbonyl-4-methylpyrrolidine-2-carboxylic acid is reacted with methyl iodide in the presence of potassium carbonate in acetonitrile solvent to give methyl (2R,4S)-1-tert-butoxycarbonyl-4-methylpyrrolidine-2-carboxylate. Methyl (2R,4S)-1-tert-butoxycarbonyl-4-methylpyrrolidine-2-carboxylate is reduced with lithium borohydride to give (2R,4S)-1-tert-butoxycarbonyl-2-hydroxymethyl-4-methylpyrrolidine. (2R,4S)-1-tert-Butoxycarbonyl-2-hydroxymethyl-4-methylpyrrolidine is reacted with 4N hydrogen chloride-dioxane to give (2R,4S)-2-hydroxymethyl-4-methylpyrrolidine hydrochloride. (2R,4S)-2-Hydroxymethyl-4-methylpyrrolidine hydrochloride is reacted with acrylonitrile to give 3-[(2R,4S)-2-hydroxymethyl-4-methylpyrrolidin-1-yl]propionitrile. In the same manner as in Example 1b (e) and using 3-[(2R,4S)-2-hydroxymethyl-4-methylpyrrolidin-1-yl]propionitrile and N,N-diethyl-2,3-dimethylbenzamide, 3-(2-(2R,4S)-2-hydroxymethyl-4-methylpyrrolidin-1-yl]ethyl)-5-methyl-2H-isoquinolin-1-one is obtained.
Sources & evidence
- ORD record
- ord-ce5d8788478a423cb0a6baea0022bfb6
- Source dataset
- uspto-grants-2008_12
- Patent number
- US07459465B2
Reaction notes
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