Trifluoroacetic acid → HCID 57947407, compound

HRID 416433Notes

Reaction equation

HRID 416433 reaction equation
C(OC(=O)[N:7]([CH2:12][C@H:13]([N:31]([C:33]([O:35]C(C)(C)C)=O)[CH3:32])[CH2:14][O:15][C:16](=[O:30])[NH:17][C:18]1[O:22][N:21]=[C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)[CH:19]=1)[CH2:8][CH:9]([F:11])[F:10])(C)(C)C.C(O)(C(F)(F)F)=O.[Cl:48][C:49]1[C:68]([F:69])=[CH:67][CH:66]=[CH:65][C:50]=1[CH2:51][NH:52]C(=O)OC1C=CC([N+]([O-])=O)=CC=1>C(Cl)Cl>[F:29][C:25]1[CH:24]=[C:23]([C:20]2[CH:19]=[C:18]([NH:17][C:16](=[O:30])[O:15][CH2:14][C@@H:13]([N:31]([CH3:32])[C:33]([NH:52][CH2:51][C:50]3[CH:65]=[CH:66][CH:67]=[C:68]([F:69])[C:49]=3[Cl:48])=[O:35])[CH2:12][NH:7][CH2:8][CH:9]([F:10])[F:11])[O:22][N:21]=2)[CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 579475384-Nitrophenyl 2-chloro-3-fluorobenzylcarbamateHCID 57948013HCID 57948013, compound

Product 1

HCID 57947407HCID 57947407, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {(S)-2-(tert-Butoxycarbonyl-methyl-amino)-3-[3-(3-fluoro-phenyl)-isoxazol-5-ylcarbamoyloxy]-propyl}-(2,2-difluoro-ethyl)-carbamic acid tert-butyl ester (291 mg, 0.62 mmol) in DCM (5 mL) was added TFA (1.0 mL). The mixture was stirred at RT for 1 h, concentrated, and dissolved in THF (10 mL). To the resulting solution were added 4-nitrophenyl 2-chloro-3-fluorobenzylcarbamate (220 mg, 0.68 mmol) and TEA (0.3 mL, 1.24 mmol) at 0° C. The resulting mixture was stirred at 0° C. for 1 h. The solvent was removed and the resulting residue was purified on RP-HPLC using a mixture of acetonitrile and water to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(2,2-difluoroethylamino)propyl 3-(3-fluorophenyl)isoxazol-5-ylcarbamate (135 mg, 39% for two steps) as white solid. LRMS (M+H+) m/z 559.2.

Workup

  1. concentrationconcentrated
  2. dissolutiondissolved in THF (10 mL)
  3. stirringThe resulting mixture was stirred at 0° C. for 1 h
  4. customThe solvent was removed
  5. customthe resulting residue was purified on RP-HPLC
  6. additiona mixture of acetonitrile and water

Sources & evidence

ORD record
ord-5dbdda135d574a889824889687f89dfc
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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