Triethylamine → Pyrimidine, 5-(bromomethyl)-2-[4-(trifluoromethoxy)phenyl]-

HRID 1496915Notes

Reaction equation

S(Cl)(C)(=O)=O.[F:6][C:7]([F:24])([F:23])[O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:20]=[CH:19][C:18]([CH2:21]O)=[CH:17][N:16]=2)=[CH:11][CH:10]=1.CCN(CC)CC.[Li+].[Br-:33]>C1COCC1.CC(C)=O>[Br:33][CH2:21][C:18]1[CH:17]=[N:16][C:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][C:7]([F:24])([F:23])[F:6])=[CH:10][CH:11]=2)=[N:20][CH:19]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Mesyl chloride (0.55 mL, 7.0 mmol) was added to a solution of alcohol 91 (0.951 g, 3.52 mmol) and Et3N (1.5 mL, 10.8 mmol) in THF (40 mL) at 0° C. and the mixture was stirred at 0° C. for 1 h. The mixture was partitioned between EtOAc and water, and the organic layer was dried and evaporated to give an oil, which was dissolved in acetone (100 mL). LiBr (6.10 g, 70.2 mmol) was added and the mixture was refluxed under N2 for 1 h, then filtered and evaporated. The residue was partitioned between EtOAc and water, and the organic layer was dried and evaporated. Column chromatography on silica gel (eluting with CH2Cl2) gave 5-(bromomethyl)-2-[4-(trifluoromethoxy)phenyl]pyrimidine (92) (1.097 g, 94%) as a white solid: mp 80-81° C.; 1H NMR (CDCl3) δ 8.82 (s, 2H), 8.50 (d, J=9.0 Hz, 2H), 7.32 (d, J=9.0 Hz, 2H), 4.48 (s, 2H). APCI MS m/z 333, 335 [M+H]+.

Workup

customThe mixture was partitioned between EtOAc and water
customthe organic layer was dried
customevaporated
customto give an oil, which
temperaturethe mixture was refluxed under N2 for 1 h
filtrationfiltered
customevaporated
customThe residue was partitioned between EtOAc and water
customthe organic layer was dried
customevaporated

Sources & evidence

ORD record: ord-fe6e8c9a86304536938ddc64d032bc5f
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09198913B2

Reaction notes

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