Ethanol → 2,4-Dichloro-6-(3-methoxyphenyl)pyrimidine

HRID 2244168Notes

Reaction equation

Cl[C:2]1[C:3]([Cl:9])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:10][O:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][CH:17]=1.C(O)C.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[Cl:8][C:5]1[N:4]=[C:3]([Cl:9])[CH:2]=[C:7]([C:16]2[CH:15]=[CH:14][CH:13]=[C:12]([O:11][CH3:10])[CH:17]=2)[N:6]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Trichloropyrimidine (11.83 g, 64.49 mmol) was added to a solution of 3-methoxyphenylboronic acid (9.8 g, 64.49 mmol) in a solvent mixture of ethanol (30 mL), toluene (30 mL) and 2M aqueous sodium bicarbonate (96.7 mL) at rt. The resulting mixture was degassed under vacuum for several min before the flask was purged with nitrogen. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II)dichloromethane adduct (2.4 g, 3.22 mmol) was added and the resulting mixture was heated for 3 h at 50° C. The cooled reaction mixture was filtered through a silica gel pad and the pad was washed with acetone. The filtrated was evaporated under reduced pressure. The crude material was purified by column chromatography eluting with a gradient of 0 to 45% ethyl acetate/hexanes to give 2,4-dichloro-6-(3-methoxy-phenyl)-pyrimidine as a white solid (14.4 g, 65.4%). MS ES 255 (M+H)+, calcd 255, RT=3.35 min.

Workup

customThe resulting mixture was degassed under vacuum for several min before the flask
customwas purged with nitrogen
customThe cooled reaction mixture
filtrationwas filtered through a silica gel pad
washthe pad was washed with acetone
customThe filtrated was evaporated under reduced pressure
customThe crude material was purified by column chromatography
washeluting with a gradient of 0 to 45% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-a972d7b75f794c2ba66644aa67a12406
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07678804B2

Reaction notes

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