Water → HCID 58573549, compound

HRID 932125Notes

Reaction equation

HRID 932125 reaction equation
[CH2:1]([C@@:4]1([CH3:37])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:34][CH3:35])[CH2:25][NH:26][S:27]([C:30]([CH3:33])([CH3:32])[CH3:31])(=[O:29])=[O:28])[C:5]1=[O:36])[CH:2]=[CH2:3].[H-].[Na+].I[CH3:41].O>CN(C=O)C>[CH2:1]([C@@:4]1([CH3:37])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[N:6]([C@@H:24]([CH2:34][CH3:35])[CH2:25][N:26]([CH3:41])[S:27]([C:30]([CH3:31])([CH3:33])[CH3:32])(=[O:28])=[O:29])[C:5]1=[O:36])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58573484HCID 58573484, compound

Product 1

HCID 58573549HCID 58573549, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-((S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butyl)-2-methylpropane-2-sulfonamide (100 mg, 0.177 mmol; Example 181, Step A) was dissolved in DMF (2.5 mL), and sodium hydride (60% dispersion in mineral oil, 19 mg, 0.45 mmol) was added in a single portion. After 25 minutes, this mixture was cooled to 0° C. in an ice-water bath, and iodomethane (0.04 mL, 0.643 mmol) was added dropwise by syringe. The mixture was allowed to gradually warm to ambient temperature, gradually becoming a pale yellow suspension. After 2 h water (2 mL) was added very carefully. The resulting mixture was partitioned between ethyl acetate and saturated aq. NH4Cl solution. The aqueous phase was back-extracted (2×) and the combined organics were washed with sat. aq. NaCl solution (2×), dried over sodium sulfate, filtered, and the filtrate was concentrated in vacuo to an oily residue that was chromatographed on a 12 g silica column, eluting with a gradient of 0 to 35% EtOAc in hexanes. Fractions containing the sulfonamide product were pooled and concentrated to give the title compound. MS (ESI) m/z=579 [M+H]+.

Workup

  1. temperatureto gradually warm to ambient temperature
  2. customThe resulting mixture was partitioned between ethyl acetate and saturated aq. NH4Cl solution
  3. extractionThe aqueous phase was back-extracted (2×)
  4. washthe combined organics were washed with sat. aq. NaCl solution (2×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated in vacuo to an oily residue that
  8. customwas chromatographed on a 12 g silica column
  9. washeluting with a gradient of 0 to 35% EtOAc in hexanes
  10. additionFractions containing the sulfonamide product
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-f3451948403c4d079f65d26354a429a9
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

Loading…