Oxolane--water (1/1) → 6-(N-(3-Chloro-4-formylphenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1424880Notes

Reaction equation

HRID 1424880 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:10]([C:15]2[C:34]([CH:35]3[CH2:37][CH2:36]3)=[CH:33][C:18]3[C:19]([C:29]([NH:31][CH3:32])=[O:30])=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[O:21][C:17]=3[CH:16]=2)[S:11]([CH3:14])(=[O:13])=[O:12])[CH:5]=[CH:6][C:7]=1[CH:8]=C.C1C[O:41]CC1.O.I([O-])(=O)(=O)=O.[Na+]>CCOC(C)=O.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[CH:3]=[C:4]([N:10]([C:15]2[C:34]([CH:35]3[CH2:37][CH2:36]3)=[CH:33][C:18]3[C:19]([C:29]([NH:31][CH3:32])=[O:30])=[C:20]([C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=4)[O:21][C:17]=3[CH:16]=2)[S:11]([CH3:14])(=[O:13])=[O:12])[CH:5]=[CH:6][C:7]=1[CH:8]=[O:41]

Participants

6

Reactant 3

HCID 21881883Oxolane--water (1/1)HCID 23667635Sodium periodateHCID 1317323266-(N-(3-Chloro-4-vinylphenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

Product 1

HCID 1317323276-(N-(3-Chloro-4-formylphenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 50%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 6-(N-(3-chloro-4-vinylphenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (890 mg, 1.65 mmol) in 1:1 THF/water (36 mL) was treated with a solution of osmium tetroxide (2.5% in t-butanol, 0.415 mL, 0.033 mmol) and stirred for a few minutes. The resulting solution was treated with sodium periodate (883 mg, 4.13 mmol) and the reaction mixture was stirred for 16 h at rt. The reaction mixture was diluted with EtOAc and washed with 1:1 water/brine (1×), then brine (1×). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was dissolved in dichloromethane, filtered and the filtrate was purified by flash chromatography (silica gel, gradient of 0 to 50% EtOAc in hexanes) to afford the title compound (0.45 g, 50%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.23 (s, 1H), 8.45-8.53 (m, 1H), 8.04 (s, 1H), 7.94-8.01 (m, 2H), 7.86 (d, 1H), 7.35-7.46 (m, 3H), 7.31 (dd, 1H), 7.24-7.29 (m, 1H), 3.57 (s, 3H), 2.84 (d, 3H), 1.89-1.98 (m, 1H), 0.68-1.02 (m, 3H), 0.42-0.58 (m, 1H). LCMS (m/z, ES+)=541 (M+H+).

Workup

  1. stirringthe reaction mixture was stirred for 16 h at rt
  2. washwashed with 1:1 water/brine (1×)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloromethane
  6. filtrationfiltered
  7. customthe filtrate was purified by flash chromatography (silica gel, gradient of 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5fe70a1d931f40e9930d60b06887c698
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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