Cyanomethylenetributylphosphorane → Methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)propanoate

HRID 932069Notes

Reaction equation

HRID 932069 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH2:22]O)[C:11](=[O:26])[C@H:10]([CH:27]([CH3:32])[C:28]([O:30][CH3:31])=[O:29])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:33][NH:34][S:35]([CH:38]1[CH2:40][CH2:39]1)(=[O:37])=[O:36].C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1.CCOC(C)=O.[Na+].[Cl-]>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH2:22][N:34]([CH3:33])[S:35]([CH:38]3[CH2:40][CH2:39]3)(=[O:37])=[O:36])[C:11](=[O:26])[C@H:10]([CH:27]([CH3:32])[C:28]([O:30][CH3:31])=[O:29])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 4622928CyanomethylenetributylphosphoraneHCID 15334537N-methylcyclopropanesulfonamide2×HCID 68000935Methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-2-oxopiperidin-3-yl)propanoate

Product 1

HCID 68000356Methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)propanoate

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 5234Sodium ChlorideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A flask, containing a solution of methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-2-oxopiperidin-3-yl)propanoate (195 mg, 0.408 mmol; Example 127, Step E) and N-methylcyclopropanesulfonamide (165 mg, 1.223 mmol) in toluene (2038 μL) was evacuated and backfilled with Ar (5×). Then cyanomethylenetributylphosphorane (321 μL, 1.223 mmol) was added. The light brownish orange mixture was heated to 70° C. for 2 h. More N-methylcyclopropanesulfonamide (134 mg, 0.991 mmol) was added and the mixture was heated to 70° C. for 2 h. The mixture was heated to reflux overnight and then cooled to room temperature. The mixture was diluted with EtOAc and sat. aq. NaCl solution. The layers were separated. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (4 g column eluent: 0 to 100% EtOAc in hexanes) to give the title compound.

Workup

  1. customwas evacuated
  2. temperaturethe mixture was heated to 70° C. for 2 h
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperaturecooled to room temperature
  6. customThe layers were separated
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (4 g column eluent: 0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e5426c202d694d4e9c33e24639803151
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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