HCID 69212799, compound → HCID 67004890, compound

HRID 1280951Notes

Reaction equation

HRID 1280951 reaction equation
ClC1C=CC(C[N:7]2[CH2:11][CH2:10][C@H:9]([NH:12][C:13](=[O:28])[CH2:14][NH:15][C:16](=[O:27])[C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=3)[CH2:8]2)=CC=1>C(O)=O.CO.[OH-].[OH-].[Pd+2]>[F:26][C:23]([F:24])([F:25])[C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[C:16]([NH:15][CH2:14][C:13]([NH:12][C@H:9]1[CH2:10][CH2:11][NH:7][CH2:8]1)=[O:28])=[O:27]

Participants

4

Reactant 1

HCID 69212799HCID 69212799, compound

Product 1

HCID 67004890HCID 67004890, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 18963719Formic acid methanolSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of (S)-1-(4-chlorobenzyl)-3-[N-{3-(trifluoromethyl)benzoyl}glycyl]aminopyrrolidine (2.93 g, 6.66 mmol) and Pd(OH)2 in 5% HCO2H/methanol (70 mL) was stirred at 60° C. for 3 h. The Pd catalyst was filtered off through Celite, and the filtrate was concentrated. To the residue was added 2N aqueous NaOH solution (100 mL) and the mixture was extracted with ethyl acetate (100 mL×3). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (SiO2, AcOEt/MeOH/Et3N=85/10/5-60/30/5) gave (S)-3-[N-{3-(trifluoromethyl)benzoyl}glycyl]aminopyrrolidine (1.70 g, 81%) as an oil: 1H NMR (CDCl3, 270 MHz) δ1.76 (d, J=7.3 Hz, 1 H), 2.07-2.25 (m, 1 H), 2.81-2.98 (m, 2 H), 3.02-3.11 (m, 2 H), 4.12 (s, 2 H), 4.41 (br, 1 H), 6.90 (br, 1 H), 7.45 (br, 1 H), 7.58 (dd, J=7.3 and 7.3 Hz, 1 H), 7.77 (d, J=7.3 Hz, 1 H), 8.02 (d, J=7.3 Hz, 1 H), 8.11 (s, 1H); ESI/MS n/e 316.0 (M++H, C14H16F3N3O2).

Workup

  1. filtrationThe Pd catalyst was filtered off through Celite
  2. concentrationthe filtrate was concentrated
  3. additionTo the residue was added 2N aqueous NaOH solution (100 mL)
  4. extractionthe mixture was extracted with ethyl acetate (100 mL×3)
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-dac476c48a7b4da5ae5a17dc0bc8303d
Source dataset
uspto-grants-2002_09
Patent number
US06451842B1

Reaction notes

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