tert-Butanol → HCID 21099527, compound

HRID 2377016Notes

Reaction equation

HRID 2377016 reaction equation
Cl[S:2]([N:5]=C=O)(=[O:4])=[O:3].C(O)(C)(C)C.C(N(CC)CC)C.Cl.[F:21][C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]2[CH:35]=[CH:34][C:33]([S:36]([C:39]3[CH:40]=[C:41]([NH2:45])[CH:42]=[CH:43][CH:44]=3)(=[O:38])=[O:37])=[CH:32][CH:31]=2)=[CH:24][CH:23]=1>ClCCl>[F:21][C:22]1[CH:23]=[CH:24][C:25](/[CH:28]=[CH:29]/[C:30]2[CH:31]=[CH:32][C:33]([S:36]([C:39]3[CH:40]=[C:41]([NH:45][S:2]([NH2:5])(=[O:4])=[O:3])[CH:42]=[CH:43][CH:44]=3)(=[O:38])=[O:37])=[CH:34][CH:35]=2)=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 21099488HCID 21099488, compound

Product 1

HCID 21099527HCID 21099527, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To dichloromethane (1 mL) at 0° C. was added chlorosulfonyl isocyanate (0.03 mL, 0.26 mmol) and tert-butanol (0.03 mL, 0.26 mmol). The mixture was stirred for 10 minutes then triethylamine (0.054 mL, 0.39 mmol) was added followed by [3-({4-[(E)-2-(4-fluorophenyl)vinyl]phenyl}sulfonyl)phenyl]amine hydrochloride (Example 212, 100 mg, 0.26 mmol). The reaction was allowed to warm to room temperature and stirred for 2 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over MgSO4 and evaporated. The residue was treated with trifluoroacetic acid for 15 minutes then evaporated. The residue was partitioned between ethyl acetate and 1M sodium hydroxide. The organic layer was washed with brine, dried over MgSO4 and evaporated. The residue was purified by flash column chromatography on silica, eluting with 50% ethyl acetate/isohexane to give the title compound (40 mg, 36%). δH (500 MHz, d6 DMSO): 9.94 (1H, s), 7.89 (2H, d, J=8.4 Hz), 7.79 (2H, d, J=8.4 Hz), 7.71-7.65 (3H, m), 7.51-7.48 (2H, m), 7.44-7.38 (2H, m), 7.30-7.20 (5H, m); m/z (ES+) 431 [MH+].

Workup

  1. stirringstirred for 2 hours
  2. customThe mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. additionThe residue was treated with trifluoroacetic acid for 15 minutes
  7. customthen evaporated
  8. customThe residue was partitioned between ethyl acetate and 1M sodium hydroxide
  9. washThe organic layer was washed with brine
  10. dry with materialdried over MgSO4
  11. customevaporated
  12. customThe residue was purified by flash column chromatography on silica
  13. washeluting with 50% ethyl acetate/isohexane

Sources & evidence

ORD record
ord-5e4eea1ccfa44cc5af8e47ec614c8260
Source dataset
uspto-grants-2008_12
Patent number
US07468393B2

Reaction notes

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