Acetic Anhydride → 2-acetylamino-N-benzyl-3-difluoromethoxy-propionamide

HRID 2096926Notes

Reaction equation

HRID 2096926 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.[C:25](OC(=O)C)(=[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 7918Acetic AnhydrideHCID 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

2-Amino-N-benzyl-3-difluoromethoxy-propionamide (195 mg, 0.80) was mixed with triethylamine (322 mg, 3.19 mmol) in THF (5 mL). Acetic anhydride (98.5 mg, 0.96 mmol) was then added and the reaction mixture was stirred for 1 hour. The mixture was then diluted with ethyl acetate and washed with water. The organic layer was dried and concentrated. The residue was purified by column chromatography using hexanes:ethyl acetate (50:50 to 0:100). The isolated product was triturated with diethyl ether to give 2-acetylamino-N-benzyl-3-difluoromethoxy-propionamide (135 mg, 59%) as a white solid. 1H NMR (300 MHz, CDCl3): δ (ppm) 7.33 (m, 5H), 6.68 (br, 1H), 6.37 (br, 1H), 6.24 (t, 1H), 4.72 (q, 1H), 4.87 (d, 2H), 4.23 (dd, 1H), 4.01 (dd, 1H), 2.05 (s, 3H).

Workup

  1. washwashed with water
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography
  5. customThe isolated product was triturated with diethyl ether

Sources & evidence

ORD record
ord-1307a85cfc8c4372bcb2a3a41416066c
Source dataset
uspto-grants-2013_05
Patent number
US08450336B2

Reaction notes

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