5-Bromo-2,4-dichloropyrimidine → (2,4-Dichloro-pyrimidin-5-yl)-(2,3-difluoro-6-methoxy-phenyl)-methanol

HRID 1435332Notes

Reaction equation

Br[C:2]1[C:3]([Cl:9])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[F:15][C:16]1[C:23]([F:24])=[CH:22][CH:21]=[C:20]([O:25][CH3:26])[C:17]=1[CH:18]=[O:19]>O1CCCC1>[Cl:8][C:5]1[N:4]=[C:3]([Cl:9])[C:2]([CH:18]([C:17]2[C:20]([O:25][CH3:26])=[CH:21][CH:22]=[C:23]([F:24])[C:16]=2[F:15])[OH:19])=[CH:7][N:6]=1

Participants

Conditions

Temperature: -30 °C

Procedure

A solution of 5-bromo-2,4-dichloropyrimidine (18.8 g, 82.5 mmol, Aldrich) in tetrahydrofuran (50 mL) was chilled to −30° C. and isopropylmagnesium chloride (41.25 mL, 82.5 mmol, 2M in tetrahydrofuran, Aldrich) was added. The mixture was stirred at −30° C. for 20 minutes and a solution of 2,3-difluoro-6-methoxybenzaldehyde (12.91 g, 75 mmol, Apollo) in tetrahydrofuran (40 mL) was added slowly at this temperature. The mixture was then stirred at 0° C. for one hour and quenched with aqueous ammonium chloride. Extraction with ethyl acetate and crystallization from ethyl ether/hexanes gave 20.5 g of rac-(2,4-dichloro-pyrimidin-5-yl)-(2,3-difluoro-6-methoxy-phenyl)-methanol as a light yellow solid, MP 99-101° C. MS(ES) MH+322

Workup

stirringThe mixture was then stirred at 0° C. for one hour
customquenched with aqueous ammonium chloride
extractionExtraction
customwith ethyl acetate and crystallization from ethyl ether/hexanes

Sources & evidence

ORD record: ord-04fd1ab8f9db4d899671ff2cfebc2554
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07615634B2

Reaction notes

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