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

HRID 2096913Notes

Reaction equation

HRID 2096913 reaction equation
[NH2:1][CH:2]([CH2:13][O:14][CH:15]([F:17])[F:16])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].C(N(CC)CC)C.[CH:25](=[O:27])[CH3:26]>C1COCC1.C(OCC)(=O)C>[C:25]([NH:1][CH:2]([CH2:13][O:14][CH:15]([F:16])[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:27])[CH3:26]

Participants

6

Reactant 3

HCID 177AcetaldehydeHCID 8471TriethylamineHCID 23649017HCID 23649017, compound

Product 1

HCID 236490162-acetylamino-N-benzyl-3-difluoromethoxy-propionamideYield 59.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-amino-N-benzyl-3-(difluoromethoxy)propanamide (195 mg, 0.798 mmol) and triethylamine (322 mg, 3.19 mmol) in THF (5 mL), acetic hydride (98.5 mg, 0.958 mmol) was added. The reaction mixture was stirred at room temperature for an hour, diluted with ethyl acetate and washed with water. The organic layer was concentrated with silica gel and purified by column chromatography, eluting with 50-100% ethyl acetate in hexanes. The product was triturated with diethyl ether to give 2-(acetylamino)-N-benzyl-3-(difluoromethoxy)propanamide (135 mg, 59%) as a white solid, MP: 173.3° C. 1H NMR (300 MHz, CDCl3): (ppm) 7.25-7.39 (m, 5H), 6.68 (w, 1H), 6.42 (d, 1H), 6.24 (wt, 1H), 4.73 (m, 1H), 4.48 (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
  4. washeluting with 50-100% ethyl acetate in hexanes
  5. customThe product was triturated with diethyl ether

Sources & evidence

ORD record
ord-2a4a3d689832441a826da6f16c0731de
Source dataset
uspto-grants-2013_05
Patent number
US08450336B2

Reaction notes

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