Dimethylformamide → Methyl 2-chloro-6-cyclopropyl-2',4'-difluoro-3-hydroxybiphenyl-4-carboxylate

HRID 531077Notes

Reaction equation

HRID 531077 reaction equation
[Cl:1]N1C(=O)CCC1=O.CN(C=O)C.[CH:14]1([C:17]2[CH:22]=[C:21]([C:23]([O:25][CH3:26])=[O:24])[C:20]([OH:27])=[CH:19][C:18]=2[C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])[CH2:16][CH2:15]1>O>[Cl:1][C:19]1[C:20]([OH:27])=[C:21]([C:23]([O:25][CH3:26])=[O:24])[CH:22]=[C:17]([CH:14]2[CH2:16][CH2:15]2)[C:18]=1[C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=1[F:35]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 31398Chlorosuccinimide2×HCID 117992303Methyl 2-cyclopropyl-2',4'-difluoro-5-hydroxybiphenyl-4-carboxylate

Product 1

HCID 117992084Methyl 2-chloro-6-cyclopropyl-2',4'-difluoro-3-hydroxybiphenyl-4-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

N-Chlorosuccinimide (1.65 g) was added at room temperature to a DMF (40 mL) solution of methyl 2-cyclopropyl-2′,4′-difluoro-5-hydroxybiphenyl-4-carboxylate (3.13 g), and the mixture was stirred at the same temperature as above for 3 hours in a nitrogen atmosphere. Then, N-chlorosuccinimide (0.549 g) was further added thereto, and the mixture was stirred at the same temperature as above for 16 hours in a nitrogen atmosphere. Water was added to the reaction mixture at room temperature, and the mixture was stirred at 0° C. for 1 hour. The deposited crystals were collected by filtration. The obtained crystals were dissolved in ethyl acetate and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure to obtain the title compound (3.17 g).

Workup

  1. stirringthe mixture was stirred at the same temperature as above for 16 hours in a nitrogen atmosphere
  2. stirringthe mixture was stirred at 0° C. for 1 hour
  3. filtrationThe deposited crystals were collected by filtration
  4. dissolutionThe obtained crystals were dissolved in ethyl acetate
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-399dcecfc6a846a4b346a6da8e92dd74
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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