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

HRID 2075337Notes

Reaction equation

HRID 2075337 reaction equation
F[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-:10])=[O:9].C(=O)([O-])[O-:46].[Cs+].[Cs+].C(O)(=O)C>CN(C=O)C>[OH:46][C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([N:16]([C:38]([O:40][C:41]([CH3:43])([CH3:42])[CH3:44])=[O:39])[CH2:17][C@@H:18]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:34])[CH3:35])[CH2:19][C:20]3[CH:21]=[CH:22][C:23]([C:26]([F:28])([F:29])[F:27])=[CH:24][CH:25]=3)=[N:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 10796Cesium carbonateHCID 57991896tert-Butyl (S)-1-(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Product 1

HCID 57991949tert-Butyl (S)-1-(5-(3-hydroxy-4-nitrophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamateYield 79.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl (S)-1-(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl-boc-amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (630 mg, 982 μmol) (prepared as described in Example 1) in 15 mL DMF were added cesium carbonate (3199 mg, 9819 μmol) and acetic acid (590 mg, 9819 μmol). The mixture was heated at 70° C. for 45 minutes. The reaction mixture was concentrated, and the resulting residue was diluted with 100 mL EtOAc. The organic phase was washed with water and saturated aqueous ammonium chloride twice and then dried over sodium sulfate. Removal of the solvent gave the compound as a tan solid (500 mg, 79%). LCMS (API-ES) m/z (%): 640.0 (100%, M++H); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13 (s, 9H) 1.54 (s, 9H) 2.84-2.94 (m, 2H) 4.23-4.31 (m, 3H) 7.47 (t, J=8.78 Hz, 3H) 7.62-7.69 (m, 3H) 8.01 (d, J=8.53 Hz, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe resulting residue was diluted with 100 mL EtOAc
  3. washThe organic phase was washed with water and saturated aqueous ammonium chloride twice
  4. dry with materialdried over sodium sulfate
  5. customRemoval of the solvent

Sources & evidence

ORD record
ord-ea9399c7c9c442e3887bc202120c1155
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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