5-Bromo-2,4-dichloropyrimidine → HCID 21070508, compound

HRID 1371746Notes

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

Participants

Conditions

Temperature: -30 °C

Procedure

A solution of 5-bromo-2,4-dichloro-pyrimidine (1.0 g, 4.4 mmol, Aldrich) was dissolved in tetrahydrofuran (50 mL), cooled to −30° C., and treated slowly with isopropylmagnesium chloride (2.2 mL, 4.4 mmol, 2M in tetrahydrofuran, Aldrich). After stirring 0.5 hour between −30° C. and −25° C., the reaction was treated with a solution of 5-fluoro-benzofuran-7-carbaldehyde (0.65 g, 0.40 mmol, Step C) in tetrahydrofuran (10 mL). The temperature was slowly raised to −10° C. and then the reaction was quenched with aqueous 20% ammonium chloride. After 0.5 hours of stirring at ambient temperature, the mixture was diluted with hexane (100 mL), washed with water and dried (Na2SO4). Removal of solvent afforded crude (2,4-dichloro-pyrimidin-5-yl)-(5-fluoro-benzofuran-7-yl)-methanol as an oil. Purification was by silica gel chromatography (50% ethyl acetate/hexane) to give 930 mg of oil (˜70%). HRMS, observed: 311.9863; Calcd for (M+H)+: 311.9869

Workup

temperatureThe temperature was slowly raised to −10° C.
customthe reaction was quenched with aqueous 20% ammonium chloride
stirringAfter 0.5 hours of stirring at ambient temperature
additionthe mixture was diluted with hexane (100 mL)
washwashed with water
dry with materialdried (Na2SO4)
customRemoval of solvent
customafforded crude (2,4-dichloro-pyrimidin-5-yl)-(5-fluoro-benzofuran-7-yl)-methanol as an oil
customPurification

Sources & evidence

ORD record: ord-55825e05825b408eb4a3daaedd0e4052
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07157455B2

Reaction notes

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