Citric Acid → N-Butyloxycarbonyl-3-(3-pyrrolidine-2-one-1-ylmethylphenyl)-5-iso-butyl-thiophene-2-sulfonamide

HRID 562555Notes

Reaction equation

HRID 562555 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([C:14]3[CH:18]=[C:17]([CH2:19][CH:20]([CH3:22])[CH3:21])[S:16][C:15]=3[S:23]([NH:26]C(C)(C)C)(=[O:25])=[O:24])[CH:11]=[CH:12][CH:13]=2)[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].B(Cl)(Cl)Cl.N1(C2C=CC=CN=2)CCCC1.Cl[C:47]([O:49][CH2:50][CH2:51][CH2:52][CH3:53])=[O:48].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH2:50]([O:49][C:47]([NH:26][S:23]([C:15]1[S:16][C:17]([CH2:19][CH:20]([CH3:21])[CH3:22])=[CH:18][C:14]=1[C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])[CH:9]=1)(=[O:25])=[O:24])=[O:48])[CH2:51][CH2:52][CH3:53]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 25135Boron TrichlorideHCID 61140Butyl chloroformateHCID 110190202-(Pyrrolidin-1-yl)pyridineHCID 670049583-(3-pyrrolidine-2-one-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide

Product 1

HCID 11957018N-Butyloxycarbonyl-3-(3-pyrrolidine-2-one-1-ylmethylphenyl)-5-iso-butyl-thiophene-2-sulfonamideYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(3-pyrrolidine-2-one-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (66.7 mg, 0.149 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 (44.1 mg, 0.297 mmol) and butyl chloroformate (189.1 μL, 1.49 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 LCMS (20-100% CH3CN in water) to give the title compound in 74% yield, over two steps, (54 mg, 0.110 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 LCMS (20-100% CH3CN in water)

Sources & evidence

ORD record
ord-3d77b314bd3841eab0a5596b725b0dfb
Source dataset
uspto-grants-2011_11
Patent number
US08067418B2

Reaction notes

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