Acetic Acid → tert-Butyl (S)-1-(5-(3-hydroxy-4-aminophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

HRID 2075338Notes

Reaction equation

HRID 2075338 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([N:16]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:17][C@@H:18]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)=[N:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O.C(O)(=O)C>CO.[Pd]>[OH:1][C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([N:16]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:17][C@@H:18]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])[CH2:19][C:20]3[CH:21]=[CH:22][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:24][CH:25]=3)=[N:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[NH2:8]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 57991949tert-Butyl (S)-1-(5-(3-hydroxy-4-nitrophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Product 1

HCID 57991851tert-Butyl (S)-1-(5-(3-hydroxy-4-aminophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamateYield 53%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

tert-Butyl (S)-1-(5-(3-hydroxy-4-nitrophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (400 mg, 625 μmol) was dissolved in 100 mL MeOH in a 500 mL round bottom flask. To this flask was added 10% Pd/C (100 mg pre-wet with water) and 1.5 mL acetic acid. The mixture was stirred under an atmosphere of hydrogen under balloon pressure for 2 hours. After filtration through a pad of celite, the solution was evaporated to dryness. The residue was re-dissolved in 150 mL EtOAc. The solution was washed with saturated ammonia chloride twice and dried over sodium sulfate. After removing the solvent, the remaining residue was subjected to silica gel column chromatograph separation using 20% to 40% EtOAc in hexane as the eluant. After removing the solvent, the desired product (200 mg, 53%) was obtained as a tan solid. LCMS (API-ES) m/z (%): 610.0 (100%, M++H); 1H NMR (400 MHz, CD3OD) δ ppm 1.21 (s, 9H) 1.55 (s, 9H) 2.80-2.95 (m, 1H) 2.95-3.06 (m, 1H) 4.00-4.25 (m, 1H) 4.25-4.57 (m, 2H) 6.77 (d, J=8.22 Hz, 1H) 7.18 (dd, J=8.02, 1.96 Hz, 1H) 7.25 (d, J=1.76 Hz, 1H) 7.44-7.53 (m, 2H) 7.60 (d, J=8.02 Hz, 2H).

Workup

  1. filtrationAfter filtration through a pad of celite
  2. customthe solution was evaporated to dryness
  3. dissolutionThe residue was re-dissolved in 150 mL EtOAc
  4. washThe solution was washed with saturated ammonia chloride twice
  5. dry with materialdried over sodium sulfate
  6. customAfter removing the solvent
  7. customthe remaining residue was subjected to silica gel column chromatograph separation
  8. customAfter removing the solvent

Sources & evidence

ORD record
ord-8ab0820be19f4451ab40a1b18b105db7
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

Loading…