Methanol → HCID 72291077, compound

HRID 238736Notes

Reaction equation

HRID 238736 reaction equation
[CH3:1][C:2]([S@:5]([NH:7][C:8]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:34])([F:33])[F:32])[CH:25]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=1)[CH2:9][C:10]([NH2:12])=[O:11])=[O:6])([CH3:4])[CH3:3].CO>N.C(O)CO.CCOC(C)=O>[CH3:4][C:2]([S:5]([NH:7][C:8]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:23])([F:21])[F:22])[CH:14]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:33])([F:34])[F:32])[CH:25]=1)[CH2:9][C:10]([NH2:12])=[O:11])=[O:6])([CH3:1])[CH3:3]

Participants

6

Reactant 2

HCID 887MethanolHCID 59458937HCID 59458937, compound

Product 1

HCID 72291077HCID 72291077, compoundYield 76.3%

Reagents, catalysts & solvents 3

HCID 174Ethylene GlycolSolventHCID 222AmmoniaSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

(R)-3-(2-methylpropan-2-ylsulfinamido)-3,3-bis(3-(trifluoromethoxy)phenyl)propanamide (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-7a7d819921084ddd985f27441e3b7ffe
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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