Ammonia → HCID 72291077, compound

HRID 1874159Notes

Reaction equation

HRID 1874159 reaction equation
C[O:2][C:3](=O)[CH2:4][C:5]([NH:28][S@@:29]([C:31]([CH3:34])([CH3:33])[CH3:32])=[O:30])([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]([F:27])([F:26])[F:25])[CH:18]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]([F:16])([F:15])[F:14])[CH:7]=1.CO.[NH3:38]>C(O)CO.CCOC(C)=O>[CH3:32][C:31]([S:29]([NH:28][C:5]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]([F:27])([F:26])[F:25])[CH:18]=1)([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]([F:16])([F:15])[F:14])[CH:7]=1)[CH2:4][C:3]([NH2:38])=[O:2])=[O:30])([CH3:34])[CH3:33]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 59458579HCID 59458579, compound

Product 1

HCID 72291077HCID 72291077, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

(R)-methyl-3-(2-methylpropan-2-ylsulfinamido)-3,3-bis(3-(trifluoromethoxy)phenyl)propanoate (prepared as described for Procedure 11, 0.70 g, 1.33 mmol) was dissolved in 8N NH3 in ethylene glycol (6 mL) at room temperature in a microwave vial. The reaction mixture was heated at 120° C. for 1200 sec, and then at 130° C. for 1200 sec under microwave irradiation. After cooling, the cap was removed, and H2O was added. The mixture was extracted with EtOAc (3×), washed with H2O and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc, then 10% MeOH in EtOAc) to give 3-(2-methylpropan-2-ylsulfinamido)-3,3-bis(3-(trifluoromethoxy)phenyl)-propanamide as white solid (0.52 g, yield: 76%) LCMS: 3.88 min [M+1] 513.28 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 7.40-7.29 (m, 3H), 7.22-7.12 (m, 3H), 7.11-7.02 (m, 2H), 6.29 (m, 2H), 5.40 (s, br, 1H), 3.78 (d, J=14.50 Hz, 1H), 3.71 (s, 2H), 3.35 (d, J=14.50 Hz, 1H), 1.21-1.28 (m, 9H).

Workup

  1. customat 130° C. for 1200 sec under microwave irradiation
  2. temperatureAfter cooling
  3. customthe cap was removed
  4. additionH2O was added
  5. extractionThe mixture was extracted with EtOAc (3×)
  6. washwashed with H2O and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (silica gel, hexanes/EtOAc

Sources & evidence

ORD record
ord-b4069f3732a84528a6d65f0a3712120e
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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