Anisole → HCID 67133040, compound

HRID 659685Notes

Reaction equation

HRID 659685 reaction equation
[C:1]([C:4]1[N:5]([CH2:9][C:10]2[CH:11]=[C:12]([C:16]3[CH:20]=[C:19]([CH2:21][CH:22]([CH3:24])[CH3:23])[S:18][C:17]=3[S:25]([NH:28]C(C)(C)C)(=[O:27])=[O:26])[CH:13]=[CH:14][CH:15]=2)[CH:6]=[CH:7][N:8]=1)(=[O:3])[CH3:2].C1(OC)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].Cl[C:48]([O:50][CH2:51][CH2:52][CH2:53][CH3:54])=[O:49]>C(O)(C(F)(F)F)=O.C(Cl)Cl.O>[CH2:51]([O:50][C:48]([NH:28][S:25]([C:17]1[S:18][C:19]([CH2:21][CH:22]([CH3:23])[CH3:24])=[CH:20][C:16]=1[C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([CH2:9][N:5]2[CH:6]=[CH:7][N:8]=[C:4]2[C:1](=[O:3])[CH3:2])[CH:11]=1)(=[O:27])=[O:26])=[O:49])[CH2:52][CH2:53][CH3:54]

Participants

8

Reactant 4

HCID 7519AnisoleHCID 10340Sodium CarbonateHCID 61140Butyl chloroformateHCID 67133227HCID 67133227, compound

Product 1

HCID 67133040HCID 67133040, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 3-[3-(2-acetylimidazol-1-ylmethyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (62.4 mg, 0.132 mmol; see step (b)) in TFA (2 mL) was added anisole (150 μL) and the reaction mixture was stirred overnight at ambient temperature. The reaction mixture was concentrated in vacuo and dried in vacuo overnight. To the crude product dissolved in CH2Cl2 (2 mL) was added Na2CO3 (302 mg, 2.85 mmol), water (0.8 mL) and butyl chloroformate (83.8 μL, 0.659 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 (5:95) as eluent to give the title compound as a white solid in 34% yield, over two steps, (23 mg, 0.0045 nmol).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customdried in vacuo overnight
  3. dissolutionTo the crude product dissolved in CH2Cl2 (2 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-c84e9b2660594fb7ae7a80dbba54c40e
Source dataset
uspto-grants-2011_12
Patent number
US08080571B2

Reaction notes

Loading…