Allyl bromide → (2S)-tert-butyl 2-((5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanoate

HRID 1048264Notes

Reaction equation

HRID 1048264 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:13][CH:12]([CH3:14])[C:11](=[O:15])[N:10]([C@@H:16]([CH2:24][CH3:25])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@@H:9]2[C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:33](Br)[CH:34]=C.[Li+].[CH3:38][Si]([N-][Si](C)(C)C)(C)C.[NH4+].[Cl-]>C1COCC1>[CH2:14]([C:12]1([CH3:38])[CH2:13][C@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[C@@H:9]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[N:10]([C@@H:16]([CH2:24][CH3:25])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:11]1=[O:15])[CH:33]=[CH2:34]

Participants

6

Reactant 4

HCID 7841Allyl bromideHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 68000014(2S)-tert-butyl 2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-5-methyl-6-oxopiperidin-1-yl)butanoate

Product 1

HCID 68000080(2S)-tert-butyl 2-((5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 10.2 g (21.4 mmol) of (2S)-tert-butyl 2-(2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-5-methyl-6-oxopiperidin-1-yl)butanoate (Example 66, Step B, mixture of diastereomers) and allyl bromide (7.24 mL, 86 mmol) in THF (210 mL) was added LHMDS, (1.0M solution in THF; 64.2 mL, 64.2 mmol) at R.T. Let it stir at R.T. for 5 min. Then the reaction mixture was heated at 50° C. for 3 h. Sat. aq. NH4Cl solution was added and the mixture was 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 residue was purified by chromatography, eluting with a gradient of 0% to 20% EtOAc in hexane, to provide the title compound as a mixture of stereoisomers at C-3.

Workup

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

Sources & evidence

ORD record
ord-77ba9f094c694eb9a4a3118d98df0a64
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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