Allyl bromide → HCID 68000542, compound

HRID 931888Notes

Reaction equation

HRID 931888 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]([CH2:23][CH3:24])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:9]2[C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:32](Br)[CH:33]=[CH2:34].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH2:34]([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:25]2[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=2)[N:10]([C@@H:15]([CH2:23][CH3:24])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:11]1=[O:14])[CH:33]=[CH2:32]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 68001176(S)-tert-butyl 2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-6-oxopiperidin-1-yl)butanoate

Product 1

HCID 68000542HCID 68000542, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1.45 g (3.14 mmol) of tert-butyl (2S)-2-((2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)-6-oxo-1-piperidinyl)butanoate (Example 1, Step F) and allyl bromide (0.326 mL, 3.76 mmol) in 12.5 mL of THF was added dropwise at −78° C. 3.3 mL of a 1 M solution of lithium bis(trimethylsilyl)-amide in THF (3.3 mmol). After being stirred at −78° C. for 3 h, the reaction was quenched with sat. aqueous NH4Cl solution, extracted with ethyl acetate. The combined organic layers were washed with 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 (50 g SiO2, eluent: 5 to 20% EtOAc/hexanes, gradient elution) provided tert-butyl (2S)-2-((3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-1-yl)butanoate as the faster eluting major isomer.

Workup

  1. customthe reaction was quenched with sat. aqueous NH4Cl solution
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with 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 (50 g SiO2, eluent: 5 to 20% EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-7435bb06c09d46f0907e6de5daee55c6
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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