Methyl acetoacetate → 5-(2-Chloro-5-trifluoromethyl-phenyl)-2-methyl-1-((R)-2-methyl-tetrahydro-furan-2-ylmethyl)-1H-pyrrole-3-carboxylic acid ((1R,2R)-2-hydroxy-cyclohexyl)-amide

HRID 229883Notes

Reaction equation

HRID 229883 reaction equation
CO[C:3](=[O:8])[CH2:4][C:5](=O)[CH3:6].Br[CH2:10][C:11]([C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[Cl:23])=O.[CH3:24][C:25]1([CH2:30][NH2:31])[CH2:29][CH2:28][CH2:27][O:26]1.[NH2:32][C@@H:33]1[CH2:38][CH2:37][CH2:36][CH2:35][C@H:34]1[OH:39]>>[OH:39][C@@H:34]1[CH2:35][CH2:36][CH2:37][CH2:38][C@H:33]1[NH:32][C:3]([C:4]1[CH:10]=[C:11]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2[Cl:23])[N:31]([CH2:30][C@@:25]2([CH3:24])[CH2:29][CH2:28][CH2:27][O:26]2)[C:5]=1[CH3:6])=[O:8]

Participants

5

Reactant 4

HCID 7757Methyl acetoacetateHCID 111269Tetrahydrofurfuryl-2-methylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 27831832-Chloro-5-(trifluoromethyl)phenacyl bromide

Product 1

HCID 116562485-(2-Chloro-5-trifluoromethyl-phenyl)-2-methyl-1-((R)-2-methyl-tetrahydro-furan-2-ylmethyl)-1H-pyrrole-3-carboxylic acid ((1R,2R)-2-hydroxy-cyclohexyl)-amide

Procedure

The title compound was synthesized in analogy to example 7, using 3-oxo-butyric acid methyl ester as compound of formula R, 2-bromo-1-[2-chloro-5-(trifluoromethyl)-phenyl]-ethanone as compound of formula S, tetrahydro-2-methyl-2-furanmethanamine as R3—(CH2)m—NH2 and (1R,2R)-2-aminocyclohexanol as R1R2NH. Enantiomers of the 5-(2-chloro-5-trifluoromethyl-phenyl)-2-methyl-1-(−2-methyl-tetrahydro-furan-2-ylmethyl)-1H-pyrrole-3-carboxylic acid methyl ester were separated on ChiralPak AD (2% isopropanol/heptane) and the (+)-enantiomer was processed to Isomer II; MS (ISP) 499.4 (M+H)+.

Workup

  1. customEnantiomers of the 5-(2-chloro-5-trifluoromethyl-phenyl)-2-methyl-1-(−2-methyl-tetrahydro-furan-2-ylmethyl)-1H-pyrrole-3-carboxylic acid methyl ester were separated on ChiralPak AD (2% isopropanol/heptane)

Sources & evidence

ORD record
ord-37ceadb9a46f4afaa1b7be2234a4bb55
Source dataset
uspto-grants-2009_07
Patent number
US07563910B2

Reaction notes

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