Hydrochloric Acid → (S)-Phenyl(1-(3-chloro-2,6-difluorophenyl)-3-oxopropyl)carbamate

HRID 516209Notes

Reaction equation

HRID 516209 reaction equation
[C:1]1([O:7][C:8](=[O:23])[NH:9][C@H:10]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[C:16]([Cl:21])[C:15]=2[F:22])[CH2:11][CH:12]=C)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.ClC(OC1C=CC=CC=1)=[O:27]>CO.C(#N)C.CCOC(C)=O>[C:1]1([O:7][C:8](=[O:23])[NH:9][C@H:10]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[C:16]([Cl:21])[C:15]=2[F:22])[CH2:11][CH:12]=[O:27])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 15891Phenyl chloroformateHCID 131733335(S)-Phenyl(1-(3-chloro-2,6-difluorophenyl)but-3-en-1-yl)carbamate

Product 1

HCID 89408383(S)-Phenyl(1-(3-chloro-2,6-difluorophenyl)-3-oxopropyl)carbamateYield 40%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-Phenyl(1-(3-chloro-2,6-difluorophenyl)but-3-en-1-yl)carbamate: To a solution of crude Intermediate 17B (1.17 g, 3.64 mmol) in MeOH (10 mL) was added HCl (5 mL, 20.00 mmol) and the reaction was stirred at rt for 1 h. After 1 h, the reaction mixture was concentrated and dried under vacuum to obtain a pale yellow solid. The solid was dissolved in ACN (25 mL) followed by addition of TEA (1.520 mL, 10.91 mmol). The above reaction mixture was cooled to 0° C. To this mixture was added phenyl chloroformate (0.502 mL, 4.00 mmol) dropwise and the resulting reaction was stirred at 0° C. for 1 h. The reaction mixture was then diluted with EtOAc and washed with water followed by brine. The crude product was then purified by silica gel chromatography to give the desired product (490 mg, 40%) as clear oil. MS (ESI) m/z: 338.1 (M+H)+.

Workup

  1. waitAfter 1 h
  2. concentrationthe reaction mixture was concentrated
  3. customdried under vacuum
  4. customto obtain a pale yellow solid
  5. customThe above reaction mixture
  6. temperaturewas cooled to 0° C
  7. customthe resulting reaction
  8. stirringwas stirred at 0° C. for 1 h
  9. washwashed with water
  10. customThe crude product was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-75fae04c41dd4972912e121f1787796b
Source dataset
uspto-grants-2015_08
Patent number
US09108981B2

Reaction notes

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