Acetic Anhydride → 2-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamide

HRID 601967Notes

Reaction equation

HRID 601967 reaction equation
C([N:8](CC1C=CC=CC=1)[CH:9]([CH2:22][O:23][CH:24]([F:26])[F:25])[C:10]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=1)=[O:11])C1C=CC=CC=1.C(N(CC)CC)C.C(OC(=O)C)(=O)C>C(O)C.ClCCl.[OH-].[OH-].[Pd+2]>[NH2:8][CH:9]([CH2:22][O:23][CH:24]([F:25])[F:26])[C:10]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=1)=[O:11]

Participants

7

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 57539235HCID 57539235, compound

Product 1

HCID 685361582-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamideYield 69.2%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

2-dibenzylamino-N-(3,4-difluoro-benzyl)-3-difluoromethoxy-propionamide (298 mg, 0.645 mmol) was stirred with 10% Pd(OH)2 (200 mg) in ethanol under H2 overnight. The reaction mixture was filtered and concentrated. The residue was mixed with triethylamine (254 mg, 2.5 mmol) in dichloromethane (2 mL) and treated with acetic anhydride (85 μL) at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane and washed with water. The organic layer was concentrated with silica gel and purified by column chromatography, eluting with 30-100% ethyl acetate in hexanes. The product was triturated with diethyl ether to give 2-amino-N-(3,4-difluorobenzyl)-3-(difluoromethoxy)propanamide (125 mg, 60%) as a white solid, MP: 146° C. 1H NMR (300 MHz, CDCl3): δ(ppm) 6.92-7.16 (m, 4H), 6.47 (d, 1H), 6.25 (wt, 1H), 4.75 (m, 1H), 4.41 (m, 2H), 4.22 (dd, 1H), 4.02 (dd, 1H) and 2.05 (s, 3H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. washwashed with water
  4. concentrationThe organic layer was concentrated with silica gel
  5. custompurified by column chromatography
  6. washeluting with 30-100% ethyl acetate in hexanes
  7. customThe product was triturated with diethyl ether

Sources & evidence

ORD record
ord-ac9bfb6e58ee4543b134e32c9af29d42
Source dataset
uspto-grants-2011_03
Patent number
US07902401B2

Reaction notes

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