Triethylamine → N-(1-(2-Bromo-4-fluorophenyl)ethyl)-2,2-difluoroacetamide

HRID 558142Notes

Reaction equation

HRID 558142 reaction equation
[F:1][CH:2]([F:6])[C:3](O)=[O:4].[Br:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[CH:15]([NH2:17])[CH3:16].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl>[Br:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[CH:15]([NH:17][C:3](=[O:4])[CH:2]([F:6])[F:1])[CH3:16]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 9788Difluoroacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 570869192-Bromo-4-fluoro-α-methylbenzenemethanamine

Product 1

HCID 57445093N-(1-(2-Bromo-4-fluorophenyl)ethyl)-2,2-difluoroacetamideYield 66.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add difluoroacetic acid (777 mg, 8.1 mmol) to a mixture of 1-(2-bromo-4-fluorophenyl)ethanamine (1.18 g, 5.4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.55 g, 8.1 mmol), 1-hydroxybenzotriazole hydrate (1.24 g, 8.1 mmol), and triethylamine (2.26 mL, 16.2 mmol) in DCM (20 mL) at 0° C. Stir the mixture at RT overnight. Dilute the mixture with DCM, wash with water and aqueous saturated sodium chloride. Separate the organic layer and dry over sodium sulfate. Filter and concentrate in vacuo. Purify the residue by column chromatography [5% to 50% ethyl acetate in hexanes] to give the title compound (1.06 g, 44%). MS (ES) m/z 296 [M+1]+.

Workup

  1. washwash with water and aqueous saturated sodium chloride
  2. customSeparate the organic layer
  3. dry with materialdry over sodium sulfate
  4. filtrationFilter
  5. concentrationconcentrate in vacuo
  6. customPurify the residue by column chromatography [5% to 50% ethyl acetate in hexanes]

Sources & evidence

ORD record
ord-f65d95b124214c7fbf1caddf6f6481ca
Source dataset
uspto-grants-2011_11
Patent number
US08063035B2

Reaction notes

Loading…