(1S,2S)-2-[(E)-3-(4-Acetylamino-4-phenyl-piperidin-1-yl)-propenyl]-1-(3,4-dichloro-phenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide → (1S,2R)-2-[3-(4-Acetylamino-4-phenyl-piperidin-1-yl)-propyl]-1-(3,4-dichlorophenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide

HRID 1172225Notes

Reaction equation

HRID 1172225 reaction equation
[F:1][C:2]1[CH:42]=[CH:41][C:5]([CH2:6][N:7]([CH3:40])[C:8]([C@@:10]2([C:32]3[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([Cl:39])[CH:33]=3)[CH2:12][C@H:11]2/[CH:13]=[CH:14]/[CH2:15][N:16]2[CH2:21][CH2:20][C:19]([NH:28][C:29](=[O:31])[CH3:30])([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:18][CH2:17]2)=[O:9])=[CH:4][CH:3]=1>ClCCl.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CC=CCCC=C1.C1C=CN=CC=1.F[P-](F)(F)(F)(F)F.[Ir]>[F:1][C:2]1[CH:42]=[CH:41][C:5]([CH2:6][N:7]([CH3:40])[C:8]([C@@:10]2([C:32]3[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([Cl:39])[CH:33]=3)[CH2:12][C@H:11]2[CH2:13][CH2:14][CH2:15][N:16]2[CH2:17][CH2:18][C:19]([NH:28][C:29](=[O:31])[CH3:30])([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:20][CH2:21]2)=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 67423469(1S,2S)-2-[(E)-3-(4-Acetylamino-4-phenyl-piperidin-1-yl)-propenyl]-1-(3,4-dichloro-phenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide

Product 1

HCID 67421530(1S,2R)-2-[3-(4-Acetylamino-4-phenyl-piperidin-1-yl)-propyl]-1-(3,4-dichlorophenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide

Reagents, catalysts & solvents 2

HCID 5702647(1,5-Cyclooctadiene)pyridine(tricyclohexylphosphine)iridium hexafluorophosphateCatalystHCID 6344DichloromethaneSolvent

Procedure

(1S,2S)-2-[(E)-3-(4-Acetylamino-4-phenyl-piperidin-1-yl)-propenyl]-1-(3,4-dichloro-phenyl)-cyclopropanecarboxylic acid (4-fluoro-benzyl)-methyl-amide (65 mg, 0.11 mmol) is dissolved in dichloromethane (10 ml). N2 is bubbled through the solution for 15 minutes before adding Crabtree's catalyst (17.7 mg, 0.022 mmol, [(1,5-cyclooctadiene)(pyridine)(tricyclohexylphosphine)iridium(I) hexafluorophosphate]). The reaction mixture is hydrogenated at a Parr apparatus (ambient temperature, 3 atm. H2) for 3 hours. The solvent is removed by evaporation and the residue is subjected to silica gel chromatography eluting with ethyl acetate:ethanol:triethylamine (95:0:5)-(85:10:5). Evaporation from heptane furnishes the title compound as a white solid. Yield 25 mg (38%).

Workup

  1. customN2 is bubbled through the solution for 15 minutes
  2. customThe solvent is removed by evaporation
  3. washeluting with ethyl acetate:ethanol:triethylamine (95:0:5)-(85:10:5)
  4. customEvaporation from heptane

Sources & evidence

ORD record
ord-4a32defa4f2a47ecaa72400e25c557ef
Source dataset
uspto-grants-2010_11
Patent number
US07834008B2

Reaction notes

Loading…