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

HRID 601965Notes

Reaction equation

HRID 601965 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): δ(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-73e0fed07d03485c9c9c0f3e58941a6c
Source dataset
uspto-grants-2011_03
Patent number
US07902401B2

Reaction notes

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