Acetaldehyde → 2-acetylamino-N-benzyl-3-difluoromethoxy-propionamide

HRID 601966Notes

Reaction equation

HRID 601966 reaction equation
[NH2:1][CH:2]([CH2:14][O:15][CH:16]([F:18])[F:17])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10](F)=[CH:9][CH:8]=1)=[O:4].C(N(CC)CC)C.[CH:26](=[O:28])[CH3:27]>C1COCC1.C(OCC)(=O)C>[C:26]([NH:1][CH:2]([CH2:14][O:15][CH:16]([F:18])[F:17])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4])(=[O:28])[CH3:27]

Participants

6

Reactant 3

HCID 177AcetaldehydeHCID 8471TriethylamineHCID 236490182-amino-3-difluoromethoxy-N-(4-fluorobenzyl)propionamide

Product 1

HCID 236490162-acetylamino-N-benzyl-3-difluoromethoxy-propionamideYield 64.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-amino-3-difluoromethoxy-N-(4-fluorobenzyl)propionamide (200 mg, 0.762 mmol) and triethylamine (293 mg, 2.9 mmol) in THF (5 mL), acetic hydride (93 mg, 0.915 mmol) was added. The reaction mixture was stirred at room temperature for three hours, diluted with ethyl acetate, and washed with water. The organic layer was concentrated with silica gel and purified by column chromatography with 50-100% ethyl acetate in hexanes. The product was triturated with diethyl ether to give 2-(acetylamino)-N-benzyl-3-(difluoromethoxy)propanamide (140 mg, 60.3%) as a white solid, MP: 130.8° C. 1H NMR (300 MHz, CDCl3): δ(ppm) 7.24 (dd, 2H), 7.03 (t, 2H), 6.73 (w, 1H), 6.41 (d, 1H), 6.24 (wt, 1H), 4.71 (m, 1H), 4.44 (d, 2H), 4.24 (dd, 1H), 4.01 (dd, 1H) and 2.05 (s, 3H).

Workup

  1. washwashed with water
  2. concentrationThe organic layer was concentrated with silica gel
  3. custompurified by column chromatography with 50-100% ethyl acetate in hexanes
  4. customThe product was triturated with diethyl ether

Sources & evidence

ORD record
ord-9c97899889c3411ca96eb22193af5649
Source dataset
uspto-grants-2011_03
Patent number
US07902401B2

Reaction notes

Loading…