Citric Acid → N-Butyloxycarbonyl-3-(3-benzoimidazol-1-ylmethylphenyl)-5-iso-butylthio-phene-2-sulfonamide

HRID 659676Notes

Reaction equation

HRID 659676 reaction equation
[N:1]1([CH2:10][C:11]2[CH:12]=[C:13]([C:17]3[CH:21]=[C:20]([CH2:22][CH:23]([CH3:25])[CH3:24])[S:19][C:18]=3[S:26]([NH:29]C(C)(C)C)(=[O:28])=[O:27])[CH:14]=[CH:15][CH:16]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.B(Cl)(Cl)Cl.N1(C2C=CC=CN=2)CCCC1.Cl[C:50]([O:52][CH2:53][CH2:54][CH2:55][CH3:56])=[O:51].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH2:53]([O:52][C:50]([NH:29][S:26]([C:18]1[S:19][C:20]([CH2:22][CH:23]([CH3:24])[CH3:25])=[CH:21][C:17]=1[C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([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:12]=1)(=[O:28])=[O:27])=[O:51])[CH2:54][CH2:55][CH3:56]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 25135Boron TrichlorideHCID 61140Butyl chloroformateHCID 110190202-(Pyrrolidin-1-yl)pyridineHCID 671329473-(3-benzoimidazol-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide

Product 1

HCID 67133392N-Butyloxycarbonyl-3-(3-benzoimidazol-1-ylmethylphenyl)-5-iso-butylthio-phene-2-sulfonamideYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(3-benzoimidazol-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (67.6 mg, 0.14 mmol; see step (a)) in CH2Cl2 (2 mL) was added BCl3 (0.6 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. Water (5 mL) was added to the residue and this was then extracted with EtOAc. The combined organic phase was washed with water and brine, dried (over anhydrous MgSO4) and concentrated in vacuo. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (41.6 mg, 0.28 mmol) and butyl chloroformate (178.4 μL, 1.40 mmol) and the reaction mixture was stirred overnight. Citric acid (3 mL, 10% aq.) was added to the reaction mixture, which was then extracted with EtOAc, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue purified by flash chromatography using MeOH:CH2Cl2 (5:95) as eluent to give the title compound in 70% yield, over two steps, (51.6 mg, 0.098 mmol).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionWater (5 mL) was added to the residue
  3. extractionthis was then extracted with EtOAc
  4. washThe combined organic phase was washed with water and brine
  5. dry with materialdried (over anhydrous MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionTo the crude product dissolved in pyridine (1.5 mL)
  8. stirringthe reaction mixture was stirred overnight
  9. extractionwas then extracted with EtOAc
  10. dry with materialdried (over anhydrous MgSO4)
  11. concentrationconcentrated in vacuo
  12. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-d45c9c1a45fe426a8aad58bab2b544ad
Source dataset
uspto-grants-2011_12
Patent number
US08080571B2

Reaction notes

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