Cyanomethylenetributylphosphorane → N-((SR)-2-((3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methoxy-2-oxopiperidin-1-yl)butyl)-N-methylcyclopropanesulfonamide

HRID 932148Notes

Reaction equation

HRID 932148 reaction equation
[CH2:1]([C@@:4]1([O:30][CH3:31])[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]([CH2:27][CH3:28])CO)[C:5]1=[O:29])[CH:2]=[CH2:3].[CH3:32][NH:33][S:34]([CH:37]1[CH2:39][CH2:38]1)(=[O:36])=[O:35].[C:40](C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[CH2:1]([C@@:4]1([O:30][CH3:31])[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]([CH:24]([CH2:27][CH3:28])[CH2:32][N:33]([CH3:40])[S:34]([CH:37]2[CH2:39][CH2:38]2)(=[O:36])=[O:35])[C:5]1=[O:29])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 4622928CyanomethylenetributylphosphoraneHCID 15334537N-methylcyclopropanesulfonamideHCID 58573388(3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methoxypiperidin-2-one

Product 1

HCID 67998474N-((SR)-2-((3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methoxy-2-oxopiperidin-1-yl)butyl)-N-methylcyclopropanesulfonamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methoxypiperidin-2-one (124 mg, 0.268 mmol; Example 203, Step D) in toluene (1.3 mL) was added N-methylcyclopropanesulfonamide (109 mg, 0.804 mmol). The mixture was evacuated and backfilled with argon (5×). Cyanomethylenetributylphosphorane (0.211 mL, 0.804 mmol) was added. The mixture was evacuated and backfilled with argon (5×). The mixture was heated in a 70° C. oil bath for 12 hours then cooled to room temperature and stirred for 2 days at room temperature. The mixture was loaded onto silica gel and the product was eluted with 20-60% ethyl acetate/hexanes. The residue was one more time purified by flash chromatography on silica gel (12 g column, eluent: 10 to 60% ethylacetate/hexanes) to afford the title compound.

Workup

  1. customThe mixture was evacuated
  2. customThe mixture was evacuated
  3. temperaturethen cooled to room temperature
  4. washthe product was eluted with 20-60% ethyl acetate/hexanes
  5. custompurified by flash chromatography on silica gel (12 g column, eluent: 10 to 60% ethylacetate/hexanes)

Sources & evidence

ORD record
ord-c8da01da06a948e6a4d2c7fd361e5e97
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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