Potassium Carbonate → HCID 118307512, compound

HRID 530402Notes

Reaction equation

HRID 530402 reaction equation
Cl[C:2]([O:4][CH2:5][CH2:6]Cl)=[O:3].[NH2:8][C:9]1[CH:10]=[C:11]([C:26]2[CH:31]=[CH:30][C:29]([C@@H:32]([OH:36])[CH:33]([F:35])[F:34])=[CH:28][CH:27]=2)[CH:12]=[C:13]([NH:15][C:16]2[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=2)[CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(OCC)(=O)C>[F:35][CH:33]([F:34])[C@@H:32]([C:29]1[CH:30]=[CH:31][C:26]([C:11]2[CH:12]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:14]=[C:9]([N:8]3[CH2:6][CH2:5][O:4][C:2]3=[O:3])[CH:10]=2)=[CH:27][CH:28]=1)[OH:36]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 123052-Chloroethyl chloroformateHCID 73295140HCID 73295140, compound

Product 1

HCID 118307512HCID 118307512, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Chloroethyl chloroformate (12.58 μL, 0.122 mmol) was slowly added to a stirred, cooled (0° C.) mixture of (1R)-1-(3′-amino-5′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-4-yl)-2,2-difluoroethanol (40 mg, 0.097 mmol) and potassium carbonate (33.7 mg, 0.244 mmol) in acetonitrile (0.5 mL). The mixture was stirred at room temperature for 1 hour. The mixture was then heated and stirred at 80° C. for 3 hours, then allowed to cool to room temperature. The mixture was diluted with ethyl acetate and concentrated in vacuo. Purification via silica gel column chromatography (20-80% ethyl acetate in hexanes) to give 3-(4′-[(1R)-2,2-difluoro-1-hydroxyethyl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-yl)-1,3-oxazolidin-2-one as a colorless solid. MS ESI calc'd. for C22H18F5N4O3 [M+H]+ 481, found 481. 1H NMR (500 MHz, DMSO-d6): δ 10.39 (s, 1H); 8.85 (d, J=4.9 Hz, 1H); 8.01 (s, 1H); 7.88 (s, 1H); 7.64 (d, J=7.8 Hz, 2H); 7.55 (t, J=8.9 Hz, 3H); 7.31 (d, J=4.8 Hz, 1H); 6.27 (d, J=4.8 Hz, 1H); 6.07 (td, J=55.5, 3.9 Hz, 1H); 4.83 (s, 1H); 4.48 (t, J=7.8 Hz, 2H); 4.13 (t, J=7.9 Hz, 2H).

Workup

  1. temperaturecooled
  2. temperatureThe mixture was then heated
  3. stirringstirred at 80° C. for 3 hours
  4. temperatureto cool to room temperature
  5. concentrationconcentrated in vacuo
  6. customPurification via silica gel column chromatography (20-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9b087dab7fa542cfbe3693e9691ade60
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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