1-(1-Methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid → HCID 58303141, compound

HRID 587354Notes

Reaction equation

HRID 587354 reaction equation
[F:1][C:2]([F:24])([F:23])[CH2:3][CH2:4][CH2:5][O:6][C:7](=[O:22])[N:8]([C@@H:10]1[C@@H:14]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:13][NH:12][CH2:11]1)[CH3:9].[CH3:25][C:26]1([C:29]([N:31]2[CH2:36][CH2:35][CH:34]([C:37]([OH:39])=[O:38])[CH2:33][CH2:32]2)=[O:30])[CH2:28][CH2:27]1>>[F:24][C:2]([F:1])([F:23])[CH2:3][CH2:4][CH2:5][O:6][C:7](=[O:22])[N:8]([C@@H:10]1[C@@H:14]([C:15]2[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=2)[CH2:13][N:12]([C:37]([CH:34]2[CH2:33][CH2:32][N:31]([C:29]([C:26]3([CH3:25])[CH2:28][CH2:27]3)=[O:30])[CH2:36][CH2:35]2)=[O:38])[CH2:11]1)[CH3:9].[F:24][C:2]([F:1])([F:23])[CH2:3][CH2:4][CH2:5][O:6][C:7](=[O:22])[N:8]([C@H:10]1[C@H:14]([C:15]2[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=2)[CH2:13][N:12]([C:37]([CH:34]2[CH2:33][CH2:32][N:31]([C:29]([C:26]3([CH3:25])[CH2:27][CH2:28]3)=[O:30])[CH2:36][CH2:35]2)=[O:39])[CH2:11]1)[CH3:9]

Participants

4

Reactant 2

HCID 594381681-(1-Methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acidHCID 67234827HCID 67234827, compound

Product 2

HCID 58303141HCID 58303141, compoundHCID 58303149HCID 58303149, compound

Procedure

In analogy to the procedure described for the synthesis of example 44 (step c), the title compounds {(3R,4S)-4-(4-chloro-phenyl)-1-[1-(1-methyl-cyclopropane carbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid 4,4,4-trifluoro-butyl ester and {(3S,4R)-4-(4-chloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid 4,4,4-trifluoro-butyl ester were prepared from [(3R,4S)-4-(4-Chloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4,4,4-trifluoro-butyl ester using 1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid instead of 1-methylcyclopropane-1-carboxylic acid and were obtained as a light brown gum. MS m/e: 558.1 [M]+. The racemate was subjected to column chromatography on chiral phase to yield {(3R,4S)-4-(4-chloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid 4,4,4-trifluoro-butyl ester (MS (m/e): 558.1 [M]+) as an off-white foam and {(3S,4R)-4-(4-chloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid 4,4,4-trifluoro-butyl ester (MS (m/e): 558.1 [M]+) as an off-white foam.

Workup

  1. customIn analogy to the procedure described for the synthesis of example 44 (step c)
  2. customwere obtained as a light brown gum

Sources & evidence

ORD record
ord-60eac0834def4e9c918bbd99e8302aeb
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

Loading…