Sodium Carbonate → N-Butyloxycarbonyl-3-[3-(2-thiophen-3-yl-imidazol-1-ylmethyl)-phenyl]-5-iso-butylthiophene-2-sulfonamide

HRID 659692Notes

Reaction equation

HRID 659692 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:7]([CH2:11][C:12]3[CH:13]=[C:14]([C:18]4[CH:22]=[C:21]([CH2:23][CH:24]([CH3:26])[CH3:25])[S:20][C:19]=4[S:27]([NH:30]C(C)(C)C)(=[O:29])=[O:28])[CH:15]=[CH:16][CH:17]=3)[CH:8]=[CH:9][N:10]=2)=[CH:2]1.B(Cl)(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].Cl[C:46]([O:48][CH2:49][CH2:50][CH2:51][CH3:52])=[O:47]>C(Cl)Cl.O>[CH2:49]([O:48][C:46]([NH:30][S:27]([C:19]1[S:20][C:21]([CH2:23][CH:24]([CH3:25])[CH3:26])=[CH:22][C:18]=1[C:14]1[CH:15]=[CH:16][CH:17]=[C:12]([CH2:11][N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)[CH:13]=1)(=[O:29])=[O:28])=[O:47])[CH2:50][CH2:51][CH3:52]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 25135Boron TrichlorideHCID 61140Butyl chloroformateHCID 671331003-[3-(2-Thiophen-3-yl-imidazol-1-ylmethyl)-phenyl]-5-iso-butyl-N-tert-butyl-thiophene-2-sulfonamide

Product 1

HCID 67133334N-Butyloxycarbonyl-3-[3-(2-thiophen-3-yl-imidazol-1-ylmethyl)-phenyl]-5-iso-butylthiophene-2-sulfonamideYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-[3-(2-thiophen-3-yl-imidazol-1-ylmethyl)-phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (38.2 mg, 0.0744 mmol; see step (a)) in CH2Cl2 (1 mL) was added BCl3 (0.2 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 CH2Cl2 (5 mL) was added Na2CO3 (35.5 mg, 0.335 mmol), water (2 mL) and butyl chloroformate (11.4 μL, 0.0893 mmol) and the reaction mixture was stirred for 5 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 (5:95) as eluent to give the title compound as a white solid in 67% yield, over two steps, (28 mg, 0.050 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 CH2Cl2 (5 mL)
  8. stirringthe reaction mixture was stirred for 5 h at ambient temperature
  9. washwashed with citric acid (10% aq), brine and water
  10. dry with materialdried (over anhydrous MgSO4)
  11. concentrationconcentrated in vacuo
  12. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-55dcbcde1e5b42fcb566666ed22f2dfd
Source dataset
uspto-grants-2011_12
Patent number
US08080571B2

Reaction notes

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