Trifluoroacetic acid → HCID 68325547, compound

HRID 2403313Notes

Reaction equation

HRID 2403313 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=3)=[C:16]([F:31])[CH:15]=2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[OH-].[Na+]>C(#N)C.O>[F:31][C:16]1[CH:15]=[C:14]([CH:10]2[O:11][CH2:12][CH2:13][NH:8][CH2:9]2)[CH:19]=[CH:18][C:17]=1[NH:20][C:21]1[N:22]=[CH:23][C:24]([C:27]([F:29])([F:30])[F:28])=[CH:25][N:26]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 68325424HCID 68325424, compound

Product 1

HCID 68325547HCID 68325547, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of (RS)-2-[3-fluoro-4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (110 mg) in acetonitrile (2 ml) and water (4 ml) was added trifluoroacetic acid (190 μl). The reaction mixture was then capped and the mixture was shaken at 80° C. for 4 h. The reaction mixture was then cooled to room temperature and poured into 1 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 (Isolute® Flash-NH2 from Separtis; gradient: heptane/EtOAc) to (RS)-(2-fluoro-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine (23 mg, 27%) as a white solid. MS (ISP): 343.1 ([M+H]+).

Workup

  1. customThe reaction mixture was then capped
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. extractionextracted twice with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis; gradient: heptane/EtOAc) to (RS)-(2-fluoro-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine (23 mg, 27%) as a white solid

Sources & evidence

ORD record
ord-b38b5d81f0e44394bab8f3a236c4f4e3
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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