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

HRID 729964Notes

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-883c1ea4adcc4a05ac342ca6e3f4de9e
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582646B2

Reaction notes

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