Trifluoroacetic acid → (R)-N-(3-fluoro-4-(morpholin-2-yl)phenyl)-5-(trifluoromethyl)pyrimidin-2-amine

HRID 2403337Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][N:10]=2)[CH:5]=[CH:4][C:3]=1[C@H:19]1[O:24][CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]1.FC(F)(F)C(O)=O.[OH-].[Na+]>C(#N)C.O>[F:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:10]=[CH:11][C:12]([C:15]([F:18])([F:16])[F:17])=[CH:13][N:14]=2)[CH:5]=[CH:4][C:3]=1[C@H:19]1[O:24][CH2:23][CH2:22][NH:21][CH2:20]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of (R)-tert-butyl 2-(2-fluoro-4-(5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)morpholine-4-carboxylate (300 mg) in acetonitrile (2 ml) and water (6 ml) was added trifluoroacetic acid (522 μl). The reaction mixture was then capped and the mixture was shaken at 80° C. for 16 h. The reaction mixture was then cooled to room temperature and poured into 4 M aq. NaOH and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (silica gel, CH2Cl2/MeOH/aq. NH3) to afford (R)—N-(3-fluoro-4-(morpholin-2-yl)phenyl)-5-(trifluoromethyl)pyrimidin-2-amine (171 mg, 74%) as an off-white solid. MS (ISP): 343.1 ([M+H]+).

Workup

customThe reaction mixture was then capped
temperatureThe reaction mixture was then cooled to room temperature
extractionextracted twice with EtOAc
dry with materialThe combined organic layers were dried over Na2SO4
concentrationconcentrated in vacuo
customThe crude material was purified by flash column chromatography (silica gel, CH2Cl2/MeOH/aq. NH3)

Sources & evidence

ORD record: ord-1bc8884cb6934e7e8a044249358b4297
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802673B2

Reaction notes

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