N-(1-(5-Fluoropyridin-2-yl)vinyl)acetamide → (S)-N-(1-(5-Fluoropyridin-2-yl)ethyl)acetamide

HRID 450355Notes

Reaction equation

HRID 450355 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11](=[O:13])[CH3:12])=[CH2:9])=[N:6][CH:7]=1>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]([NH:10][C:11](=[O:13])[CH3:12])[CH3:9])=[N:6][CH:7]=1

Participants

3

Reactant 1

HCID 66736029N-(1-(5-Fluoropyridin-2-yl)vinyl)acetamide2×

Product 1

HCID 66735550(S)-N-(1-(5-Fluoropyridin-2-yl)ethyl)acetamideYield 88%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of N-(1-(5-fluoropyridin-2-yl)vinyl)acetamide (Intermediate 2, 11.0 g, 61.1 mmol) in MeOH (120 ml) under N2 was added (+)-1,2-bis((2S,5S)-2,5-diethylphospholano)benzene(cyclooctadiene)rhodium(I)trifluoromethanesulfonate (0.441 g, 0.611 mmol). The solution was transferred to a high pressure bomb and charged 150 psi H2. The reaction stirred at room temperature and maintained inside pressure between 120-150 psi for 7 hours. The solvent was removed and the resulted residue was purified by column chromatography (EtOAc) to give the title compound as a white solid (9.8 g, 88%). 1H NMR (400 MHz) δ 8.49 (d, J=2.4 Hz, 1H), 8.32 (d, J=7.6 Hz, 1H), 7.66 (m, 1H), 7.39 (dd, J=4.4 and 8.8 Hz, 1H), 4.95 (m, 1H), 1.85 (s, 3H), 1.34 (d, J=7.2 Hz, 3H). MS: Calculated: 182. Found: [M+H]+ 183. Enantiomeric excess determined by HPLC (Chiralpak IA; 70:30 CO2/MeOH), 95.3% ee.

Workup

  1. additioncharged 150 psi H2
  2. temperaturemaintained inside pressure between 120-150 psi for 7 hours
  3. customThe solvent was removed
  4. customthe resulted residue was purified by column chromatography (EtOAc)

Sources & evidence

ORD record
ord-f9dbfaa0b139497d85e8c91a0597b07c
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Reaction notes

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