Methyl 2-[(tert-butoxycarbonyl)amino]-4-cyano-4-(2,3-difluorophenyl)butanoate → tert-butyl[(3S,5S)-5-(2,3-difluorophenyl)-2-oxopiperidin-3-yl]carbamate

HRID 1404503Notes

Reaction equation

HRID 1404503 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:14][CH:15]([C:24]#[N:25])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=1[F:23])[C:10](OC)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:14][C@@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=2[F:23])[CH2:24][NH:25][C:10]1=[O:11])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 68748709Methyl 2-[(tert-butoxycarbonyl)amino]-4-cyano-4-(2,3-difluorophenyl)butanoate

Product 1

HCID 69096669tert-butyl[(3S,5S)-5-(2,3-difluorophenyl)-2-oxopiperidin-3-yl]carbamate

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of methyl 2-[(tert-butoxycarbonyl)amino]-4-cyano-4-(2,3-difluorophenyl)butanoate (11.0 g, 31.0 mmol) in methanol (621 mL) was added palladium hydroxide on carbon powder (20% palladium, with moisture ca 60%) (5.45 g, 3.10 mmol). The mixture was pressurized to 50 psi under an atmosphere of hydrogen. After 90 min, the mixture was filtered and concentrated. Purification by chromatography (Chiral Pak® AD® column, 60% ethanol/hexanes with 0.1% diethylamine) gave the title compound. MS: m/z=349.3 (M+Na). 1H NMR (500 MHz, CDCl3): δ 7.11-6.96 (m, 3H); 5.87 (s, 1H); 5.47 (s, 1H); 4.22-4.16 (m, 1H); 3.63-3.52 (m, 2H); 3.38 (t, J=11.2 Hz, 1H); 2.70 (s, 1H); 2.09 (q, J=12.3 Hz, 1H); 1.45 (s, 9H).

Workup

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated
  3. customPurification by chromatography (Chiral Pak® AD® column, 60% ethanol/hexanes with 0.1% diethylamine)

Sources & evidence

ORD record
ord-5db9f2f01a744abe92e99a76b8b49767
Source dataset
uspto-grants-2014_12
Patent number
US08912210B2

Reaction notes

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