Tetrahydrofuran → 4-(3-Chloro-4-fluoro-phenyl)-2-methoxy-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine

HRID 230944Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[CH:9]=2)[CH:5]=[C:4]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:25]=[CH:24][N:23]=3)[CH2:18][CH2:17]2)[N:3]=1.[O:32]1CCC[CH2:33]1.C[O-].[Na+]>CO>[Cl:15][C:10]1[CH:9]=[C:8]([C:6]2[CH:5]=[C:4]([N:16]3[CH2:21][CH2:20][N:19]([C:22]4[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:25]=[CH:24][N:23]=4)[CH2:18][CH2:17]3)[N:3]=[C:2]([O:32][CH3:33])[N:7]=2)[CH:13]=[CH:12][C:11]=1[F:14]

Participants

Conditions

Temperature: 60 °C

Procedure

Combine a mixture of 2-chloro-4-(3-chloro-4-fluoro-phenyl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine (47 mg, 1 mmol), tetrahydrofuran (1 mL), and a 21% solution of sodium methoxide in MeOH (0.5 mL). Let the reaction stir at 60° C. for 16 hours. Evaporate the mixture, add water (5 mL), and extract twice with EtOAc (5 mL each). Combine the organic layers, dry (Na2SO4), and purify by preparative TLC (8:1 hexanes/EtOAc) to obtain 4-(3-chloro-4-fluoro-phenyl)-2-methoxy-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine.

Workup

customEvaporate the mixture
additionadd water (5 mL)
extractionextract twice with EtOAc (5 mL each)
dry with materialCombine the organic layers, dry (Na2SO4)
custompurify by preparative TLC (8:1 hexanes/EtOAc)

Sources & evidence

ORD record: ord-f26c304cc69545aa947259e5824aa4c6
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07566712B2

Reaction notes

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