Trifluoroacetic acid → 4-Chloro-6-(2,2,2-trifluoro-1-(3'-fluorobiphenyl-4-yl)ethoxy)pyrimidin-2-amine

HRID 419254Notes

Reaction equation

[F:1][C:2]([F:19])([F:18])[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:7][CH:6]=1)[OH:4].[H-].[Na+].[NH2:22][C:23]1[N:28]=[C:27](Cl)[CH:26]=[C:25]([Cl:30])[N:24]=1.C(O)(C(F)(F)F)=O>C1COCC1>[Cl:30][C:25]1[CH:26]=[C:27]([O:4][CH:3]([C:5]2[CH:10]=[CH:9][C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=3)=[CH:7][CH:6]=2)[C:2]([F:1])([F:18])[F:19])[N:28]=[C:23]([NH2:22])[N:24]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To 2,2,2-trifluoro-1-(3′-fluorobiphenyl-4-yl)ethanol (1.4 g, 5.18 mmol) in THF (50 mls) at 0° C. was added NaH (60% in mineral oil, 0.31 g, 7.77 mmol). The ice bath was removed and the mixture was stirred for 30 minutes. 2-Amino-4,6-dichloropyrimidine (1.0 g, 6.22 mmol) in THF (25 mls) was added at once. The mixture was heated to 50° C. for 5 hours. The reaction was complete by LCMS (Sunfire, TFA). The mixture was cooled, quenched with brine, and extracted 3 times with CH2Cl2. The organics were combined, washed with brine, dried over MgSO4, and concentrated. Chromatography (SiO2, CH2Cl2) afforded 1.48 g of 4-chloro-6-(2,2,2-trifluoro-1-(3′-fluorobiphenyl-4-yl)ethoxy)pyrimidin-2-amine. Yield 73%.

Workup

customThe ice bath was removed
temperatureThe mixture was cooled
customquenched with brine
extractionextracted 3 times with CH2Cl2
washwashed with brine
dry with materialdried over MgSO4
concentrationconcentrated

Sources & evidence

ORD record: ord-3276008758b845f19f5c5702f188abfa
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093291B2

Reaction notes

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