Allyl bromide → (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-3-methylpiperidin-2-one

HRID 1048268Notes

Reaction equation

HRID 1048268 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]([CH2:28][CH3:29])[CH2:22][O:23][CH2:24][CH:25]3[CH2:27][CH2:26]3)[C:11](=[O:30])[CH:10]([CH3:31])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH2:32](Br)[CH:33]=C.[Li+].[CH3:37][Si]([N-][Si](C)(C)C)(C)C.[NH4+].[Cl-]>C1COCC1>[CH2:31]([C@@:10]1([CH3:37])[CH2:9][C@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[C@@H:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[N:12]([C@@H:21]([CH2:28][CH3:29])[CH2:22][O:23][CH2:24][CH:25]2[CH2:27][CH2:26]2)[C:11]1=[O:30])[CH:32]=[CH2:33]

Participants

6

Reactant 4

HCID 7841Allyl bromideHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 67999671(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-3-methylpiperidin-2-one

Product 1

HCID 67999039(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.2 g (0.434 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-3-methylpiperidin-2-one (Example 68, Step C, mixture of diastereomers) and allyl bromide (0.147 mL, 1.737 mmol) in THF (5 mL) was added LHMDS, (1.0M solution in THF, 1.3 mL, 1.3 mmol) at RT. Let it stir at RT for 5 min. Then the reaction mixture was heated at 50° C. for 3 h. The reaction mixture was diluted with satd. NH4Cl. and extracted with CH2Cl2. The combined organic layers were washed with water and sat. aq. NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The crude material was purified by chromatography, eluting with a gradient of 0% to 20% EtOAc in hexane, to provide the title compound as a colorless oil.

Workup

  1. temperatureThen the reaction mixture was heated at 50° C. for 3 h
  2. additionThe reaction mixture was diluted with satd
  3. extractionand extracted with CH2Cl2
  4. washThe combined organic layers were washed with water and sat. aq. NaCl solution
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe crude material was purified by chromatography
  9. washeluting with a gradient of 0% to 20% EtOAc in hexane

Sources & evidence

ORD record
ord-b89b24fb753543b28086f5ca2cd9ef30
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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