Anisole → N-Butyloxycarbonyl-3-{3-[2-(2-ethylimidazol-1-yl)acetyl]phenyl}-5-iso-butyl-thiophene-2-sulfonamide

HRID 659700Notes

Reaction equation

HRID 659700 reaction equation
[CH2:1]([C:3]1[N:4]([CH2:8][C:9]([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)=[O:10])[CH:5]=[CH:6][N:7]=1)[CH3:2].C1(OC)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].Cl[C:49]([O:51][CH2:52][CH2:53][CH2:54][CH3:55])=[O:50]>C(O)(C(F)(F)F)=O.C(Cl)Cl.O>[CH2:52]([O:51][C:49]([NH:29][S:26]([C:18]1[S:19][C:20]([CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:21][C:17]=1[C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([C:9](=[O:10])[CH2:8][N:4]2[CH:5]=[CH:6][N:7]=[C:3]2[CH2:1][CH3:2])[CH:12]=1)(=[O:28])=[O:27])=[O:50])[CH2:53][CH2:54][CH3:55]

Participants

8

Reactant 4

HCID 7519AnisoleHCID 10340Sodium CarbonateHCID 61140Butyl chloroformateHCID 671329483-{3-[2-(2-Ethylimidazol-1-yl)acetyl]phenyl}-5-iso-butyl-N-tert-butylthio-phene-2-sulfonamide

Product 1

HCID 67133138N-Butyloxycarbonyl-3-{3-[2-(2-ethylimidazol-1-yl)acetyl]phenyl}-5-iso-butyl-thiophene-2-sulfonamideYield 47%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 3-{3-[2-(2-ethylimidazol-1-yl)acetyl]phenyl}-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (74.5 mg, 0.153 mmol; see step (b)) in TFA (3 mL) was added anisole (150 μL) and the reaction mixture was stirred for 28 h at ambient temperature. The reaction mixture was concentrated in vacuo and dried in vacuo overnight. To the crude product dissolved in CH2Cl2 (7 mL) was added Na2CO3 (72.9 mg, 0.688 mmol), water (2 mL) and butyl chloroformate (33.0 μL, 0.260 mmol), and the reaction mixture was stirred overnight 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 (8:92) as eluent to give the sub-title compound in 47% yield, over two steps, (38.5 mg, 0.0724 mmol).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customdried in vacuo overnight
  3. dissolutionTo the crude product dissolved in CH2Cl2 (7 mL)
  4. stirringthe reaction mixture was stirred overnight at ambient temperature
  5. washwashed with citric acid (10% aq), brine and water
  6. dry with materialdried (over anhydrous MgSO4)
  7. concentrationconcentrated in vacuo
  8. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-d826f5e7961f4a589d52b59ce5f12f34
Source dataset
uspto-grants-2011_12
Patent number
US08080571B2

Reaction notes

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