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

HRID 1048209Notes

Reaction equation

HRID 1048209 reaction equation
[CH2:1]([C@H:4]1[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])[CH2:25][OH:26])[C:5]1=[O:29])[CH:2]=[CH2:3].[H-].[Na+].Br[CH2:33][CH:34]1[CH2:36][CH2:35]1>CN(C=O)C>[CH2:1]([C@H:4]1[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]([CH2:27][CH3:28])[CH2:25][O:26][CH2:33][CH:34]2[CH2:36][CH2:35]2)[C:5]1=[O:29])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 58573719(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one

Product 1

HCID 67999269(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((R)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one (98 mg, 0.227 mmol) in DMF (1.10 mL) was added 60% sodium hydride in mineral oil (27.2 mg, 0.680 mmol) at 0° C. After being stirred at 0° C. for 2 min, (bromomethyl)cyclopropane (47.3 μL, 0.680 mmol) was added. The mixture was stirred at 0° C. for 2 h and then warmed to rt. Then the reaction was stirred at rt overnight. The reaction was quenched (sat aq. NH4Cl), extracted (2×EtOAc) and washed (sat. aq. NaCl solution). The combined organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography on silica gel (10% to 20% EtOAc/Hexanes gradient) provided (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((R)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one as the less polar isomer and the title compound as the more polar stereoisomer.

Workup

  1. stirringThe mixture was stirred at 0° C. for 2 h
  2. temperaturewarmed to rt
  3. stirringThen the reaction was stirred at rt overnight
  4. customThe reaction was quenched (sat aq. NH4Cl)
  5. extractionextracted (2×EtOAc)
  6. washwashed (sat. aq. NaCl solution)
  7. dry with materialThe combined organic layer was dried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customPurification by chromatography on silica gel (10% to 20% EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-c236b4461129431d87303793a8c82cba
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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