Sodium hydride → (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-(pentan-3-yl)piperidin-2-one

HRID 931969Notes

Reaction equation

HRID 931969 reaction equation
[CH2:1]([C@@:4]1([CH3:25])[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)[NH:6][C:5]1=[O:24])[CH:2]=[CH2:3].[H-].[Na+]>BrC(CC)CC>[CH2:1]([C@@:4]1([CH3:25])[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]([CH:1]([CH2:4][CH3:5])[CH2:2][CH3:3])[C:5]1=[O:24])[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 58574008(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one

Product 1

HCID 58573148(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-(pentan-3-yl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 157383-BromopentaneSolvent2×

Conditions

Temperature
120 °C

Procedure

To a suspension of 1.81 g (4.8 mmol) of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one (Example 71, Step D) in 3-bromopentane (17.6 mL) added 967 mg (60 wt. % in mineral oil, 24.2 mmol) of sodium hydride. The resulting milky white slurry was heated at 120° C. for 20 h, and then more 3-bromopentane (5.1 mL) was added. After an additional 24 h at 120° C., the reaction was cooled to room temperature and quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate (3×) and the combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (2 to 26% EtOAc/hexanes, gradient elution) provided the title compound as a white solid.

Workup

  1. temperaturethe reaction was cooled to room temperature
  2. customquenched with saturated aqueous ammonium chloride
  3. extractionThe mixture was extracted with ethyl acetate (3×)
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customPurification of the residue by flash chromatography on silica gel (2 to 26% EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-86d81841b2a0458283fe4ca9bbe41c9a
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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