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

HRID 2096914Notes

Reaction equation

HRID 2096914 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): (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-091e8a21424647e192cf5d3560dbfbe6
Source dataset
uspto-grants-2013_05
Patent number
US08450336B2

Reaction notes

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