Sodium Carbonate → N-Butyloxycarbonyl-3-[3-(2-benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-thiophene-2-sulfonamide

HRID 659705Notes

Reaction equation

HRID 659705 reaction equation
[N:1]1([CH2:10][C:11]([C:13]2[CH:14]=[C:15]([C:19]3[CH:23]=[C:22]([CH2:24][CH:25]([CH3:27])[CH3:26])[S:21][C:20]=3[S:28]([NH:31]C(C)(C)C)(=[O:30])=[O:29])[CH:16]=[CH:17][CH:18]=2)=[O:12])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.B(Cl)(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].Cl[C:47]([O:49][CH2:50][CH2:51][CH2:52][CH3:53])=[O:48]>C(Cl)Cl.O>[CH2:50]([O:49][C:47]([NH:31][S:28]([C:20]1[S:21][C:22]([CH2:24][CH:25]([CH3:27])[CH3:26])=[CH:23][C:19]=1[C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([C:11](=[O:12])[CH2:10][N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=[CH:2]2)[CH:14]=1)(=[O:29])=[O:30])=[O:48])[CH2:51][CH2:52][CH3:53]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 25135Boron TrichlorideHCID 61140Butyl chloroformateHCID 671328723-[3-(2-Benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide

Product 1

HCID 56965019N-Butyloxycarbonyl-3-[3-(2-benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-thiophene-2-sulfonamideYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-[3-(2-Benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (67.3 mg, 0.151 mmol; see step (b)) in CH2Cl2 (1 mL) was added BCl3 (0.3 mL, 1.0 M in hexane) and the reaction mixture was stirred for 1 h at ambient temperature. The reaction mixture was concentrated in vacuo. CH2Cl2 (30 mL) was added to the residue and this was washed with water. The organic phase was dried (over anhydrous MgSO4), concentrated in vacuo. To the crude product dissolved in CH2Cl2 (5 mL) was added Na2CO3 (72 mg, 0.680 mmol), water (2 mL) and butyl chloroformate (24.9 μL, 0.196 mmol), and the reaction mixture was stirred for 2 h at ambient temperature. The reaction mixture was diluted with CH2Cl2 (30 mL) and washed with citric acid (10% aq), brine and water, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue purified by flash chromatography using MeOH:CH2Cl2 (6:94) as eluent to give the title compound in 90% yield, over two steps, (66.2 mg, 0.135 mmol).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionCH2Cl2 (30 mL) was added to the residue
  3. washthis was washed with water
  4. dry with materialThe organic phase was dried (over anhydrous MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionTo the crude product dissolved in CH2Cl2 (5 mL)
  7. stirringthe reaction mixture was stirred for 2 h at ambient temperature
  8. washwashed with citric acid (10% aq), brine and water
  9. dry with materialdried (over anhydrous MgSO4)
  10. concentrationconcentrated in vacuo
  11. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-ef22710051f14bd5944f238fcaafabaf
Source dataset
uspto-grants-2011_12
Patent number
US08080571B2

Reaction notes

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