Trifluoroacetic acid → HCID 68325413, compound

HRID 2403304Notes

Reaction equation

HRID 2403304 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]([O:27][CH2:28][CH3:29])=[CH:23][N:22]=3)=[C:16]([F:30])[CH:15]=2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.CCOC(C)=O>C(#N)C.O>[CH2:28]([O:27][C:24]1[CH:23]=[N:22][C:21]([NH:20][C:17]2[CH:18]=[CH:19][C:14]([CH:10]3[O:11][CH2:12][CH2:13][NH:8][CH2:9]3)=[CH:15][C:16]=2[F:30])=[N:26][CH:25]=1)[CH3:29]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 68325477HCID 68325477, compound

Product 1

HCID 68325413HCID 68325413, compoundYield 109.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of (RS)-2-[4-(5-ethoxy-pyrimidin-2-ylamino)-3-fluoro-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (12 mg) in acetonitrile (1.5 ml) and water (3 ml) was added trifluoroacetic acid (22.0 μl). The reaction mixture was then capped and the mixture was shaken at 80° C. for 3.5 h. The reaction mixture was then cooled to room temperature and poured into EtOAc and washed with 1 M aq. NaOH. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis; gradient: heptane/EtOAc/MeOH) to afford (RS)-(5-ethoxy-pyrimidin-2-yl)-(2-fluoro-4-morpholin-2-yl-phenyl)-amine (10 mg, quant.) as an off-white solid. MS (ISP): 319.2 ([ M+H]+).

Workup

  1. customThe reaction mixture was then capped
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. washwashed with 1 M aq. NaOH
  4. dry with materialThe organic layer was 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/MeOH)

Sources & evidence

ORD record
ord-20e75ec08fe243eea03ff6635fba3b15
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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