HCID 57236775, compound → HCID 20672366, compound

HRID 1386771Notes

Reaction equation

HRID 1386771 reaction equation
COC1C=CC(C[O:8][C:9](=[O:46])[C@H:10]([N:17]2[CH2:21][C@H:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C@@H:19]([CH2:28][N:29]3[CH2:34][CH2:33][CH:32]([CH2:35][CH2:36][C:37]([F:45])([F:44])[C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[CH2:31][CH2:30]3)[CH2:18]2)[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=CC=1>C(O)C.[OH-].[OH-].[Pd+2]>[F:45][C:37]([F:44])([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[CH2:36][CH2:35][CH:32]1[CH2:31][CH2:30][N:29]([CH2:28][C@@H:19]2[C@@H:20]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:21][N:17]([C@H:10]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]([OH:46])=[O:8])[CH2:18]2)[CH2:34][CH2:33]1

Participants

4

Reactant 1

HCID 57236775HCID 57236775, compound

Product 1

HCID 20672366HCID 20672366, compoundYield 98.5%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst2×HCID 702EthanolSolvent

Procedure

2-(R)-(3-(S)-((4-(3,3-Difluoro-3-phenylpropyl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid (4-methoxy)benzyl ester (32 mg, 0.049 mmol) dissolved in 95% ethanol (2.5 mL) was hydrogenated at atmospheric pressure using 20% Pd(OH)2/C (5.8 mg). After 3 h, additional Pd(OH)2/C (3.5 mg) was added and the reaction was continued for 1 h. The mixture was filtered, the catalyst was washed with 95% ethanol, and the filtrate was evaporated. The crude product was purified by flash column chromatography on silica gel packed in CH2Cl2. Elution with 95:5:1 v/v/v CH2Cl2/CH3OH/NH4OH followed by 90:10:1 v/v/v CH2Cl2/CH3OH/NH4OH gave 26 mg of the title compound as a colorless brittle glass: RF: 0.5 (10% CH3OH/2% conc. aq. NH4OH/CH2Cl2). 1H NMR (400 MHz, CD3OD) δ 7.48-7.30 (m, 4H), 7.38-7.30 (m, 4H), 7.30-7.23 (m, 1H), 3.62-3.51 (m, 2H), 3.44 (d, J=4, 11), 3.10 (td, J=10, 8, 1H), 2.88 (bd, J=12, 1H), 2.73 (bd, J=10, 2H), 2.46 (dd, J=12, 10, 1H), 2.30 (dd, J=13,4, 1H), 2.11 (tm, J=16, 2H), 1.96 (bt, J=12, 1H), 1.90-1.64 (m, 8H), 1.59 (bt, J=12, 2H), 1.50-1.00 (m, 11H); ESI-MS 539 (M+H).

Workup

  1. waitthe reaction was continued for 1 h
  2. filtrationThe mixture was filtered
  3. washthe catalyst was washed with 95% ethanol
  4. customthe filtrate was evaporated
  5. customThe crude product was purified by flash column chromatography on silica gel
  6. washElution with 95:5:1 v/v/v CH2Cl2/CH3OH/NH4OH

Sources & evidence

ORD record
ord-c83db4f609c2472284ef066956043103
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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