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

HRID 1048207Notes

Reaction equation

HRID 1048207 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:13][CH2:12][C:11](=[O:14])[N:10]([C@@H:15]([CH2:21][CH3:22])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[C@@H:9]2[C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:30](Br)[CH:31]=[CH2:32].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH2:32]([C@H:12]1[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:23]2[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=2)[N:10]([C@@H:15]([CH2:21][CH3:22])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:11]1=[O:14])[CH:31]=[CH2:30]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 60154117(S)-Ethyl 2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-6-oxopiperidin-1-yl)butanoate

Product 1

HCID 60154134(S)-Ethyl 2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-1-yl)butanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.62 g (1.4 mmol) of (S)-ethyl 2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-6-oxopiperidin-1-yl)butanoate (Example 9, Step A) and allyl bromide (0.14 ml, 1.7 mmol) in THF (6.0 mL, 0.25 M) was added lithium bis(trimethylsilyl)-amide (1M solution in THF, 1.5 ml, 1.5 mmol) at −78° C. The reaction was allowed to warm to R.T., then was quenched (sat. aqueous NH4Cl) and extracted with EtOAc. The combined organic layers were washed with water and sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography on silica gel (15 to 20% EtOAc/Hex, gradient elution) provided the title compound as the slower eluting isomer as a colorless oil.

Workup

  1. customwas quenched (sat. aqueous NH4Cl)
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with water and sat. NaCl solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customPurification of the residue by flash chromatography on silica gel (15 to 20% EtOAc/Hex, gradient elution)

Sources & evidence

ORD record
ord-57e44248b8f246629ffc1f8b2d38b22e
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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