Hydrochloric Acid → N-(3-Chloro-2-fluoro-benzyl)-acrylamide

HRID 1527353Notes

Reaction equation

HRID 1527353 reaction equation
[F:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][NH2:5].[C:11](Cl)(=[O:14])[CH:12]=[CH2:13].Cl>C1COCC1.CCOC(C)=O>[Cl:10][C:9]1[C:2]([F:1])=[C:3]([CH:6]=[CH:7][CH:8]=1)[CH2:4][NH:5][C:11](=[O:14])[CH:12]=[CH2:13]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 13140Acryloyl chlorideHCID 2773614(3-Chloro-2-fluorophenyl)methanamine

Product 1

HCID 68283248N-(3-Chloro-2-fluoro-benzyl)-acrylamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 2-fluoro-3-chlorobenzylamine (1 g, 6.27 mmol) and TEA (1.05 mL, 7.52 mmol) in THF (20.9 mL) was added acryloyl chloride (0.61 mL, 7.52 mmol) dropwise and the reaction mixture was stirred at 23° C. for 2 h. The reaction mixture was diluted in EtOAc, HCl 1N was added and the layers separated. The aqueous layer was extracted again with EtOAc and the combined organic layers were dried, filtered and concentrated to dryness. The crude residue was purified by flash column chromatography on silica gel (xyclohexane/EtOAc gradient 100:0 to 1:1) to give the desired material. TLC, Rf (c-hexane/EtOAc 5:5)=0.41; MS (LC/MS): 214.0 [M+H]+; tR (HPLC conditions b): 3.35 min.

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted again with EtOAc
  3. customthe combined organic layers were dried
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe crude residue was purified by flash column chromatography on silica gel (xyclohexane/EtOAc gradient 100:0 to 1:1)

Sources & evidence

ORD record
ord-ac1823669f5549fba2051c1fe29970e3
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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