Sodium Carbonate → 2-(2-Chloro-2',6'-difluoro-4'-methoxybiphenyl-4-yl)acetic acid

HRID 1930107Notes

Reaction equation

Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[F:11].[Cl:12][C:13]1[CH:18]=[C:17]([CH2:19][C:20]([O:22]C)=[O:21])[CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:12][C:13]1[CH:18]=[C:17]([CH2:19][C:20]([OH:22])=[O:21])[CH:16]=[CH:15][C:14]=1[C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[F:11]

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of 4-bromo-3,5-difluoroanisole (645 mg, 2.89 mmol) and 2-chloro-4-(2-methoxy-2-oxoethyl)phenylboronic acid (Intermediate 2-6; 859 mg, 3.76 mmol) and sodium carbonate (2.89 mL, 5.78 mmol), tetrakis(triphenylphosphine)palladium(0) (207 mg, 0.18 mmol) in DME (20 mL) was degassed and then stirred at 85° C. for 17 hours. The reaction mixture was allowed to cool, evaporated and partitioned between EtOAc (75 mL), water (40 mL) and saturated brine (15 mL), The aqueous phase was acidified with 2M HCl and extracted into EtOAc (2×125 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford 2-(2-chloro-2′,6′-difluoro-4′-methoxybiphenyl-4-yl)acetic acid (654 mg, 72.4%) as a white solid, which was used without further purification.

Workup

temperatureto cool
customevaporated
custompartitioned between EtOAc (75 mL), water (40 mL) and saturated brine (15 mL)
extractionextracted into EtOAc (2×125 mL)
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-4811505286454c2d8e25c9b85377ff83
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188092B2

Reaction notes

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