Allyl bromide → (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-one

HRID 1048230Notes

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]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:11](=[O:25])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH2:26](Br)[CH:27]=[CH2:28].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH2:28]([C@H:10]1[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:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=2)[N:12]([CH2:21][CH:22]2[CH2:24][CH2:23]2)[C:11]1=[O:25])[CH:27]=[CH2:26]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-one (1481 mg, 3957 μmol; Example 35, Step A) and allyl bromide (360 μl, 4155 μmol) in THF (16 mL, 0.25 M) was added dropwise lithium bis(trimethylsilyl)amide (1M solution in THF, 4352 μl, 4352 μmol) at −78° C. After being stirred at −78° C. for 3 h, the reaction was quenched (sat. aqueous NH4Cl), extracted (2×EtOAc). The combined organic layers were washed with sat. aq. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by flash chromatography (SiO2, 20 to 30% EtOAc/Hex, gradient elution) provided the title compound as a mixture of stereoisomers.

Workup

customthe reaction was quenched (sat. aqueous NH4Cl)
extractionextracted (2×EtOAc)
washThe combined organic layers were washed with sat. aq. NaCl solution
dry with materialdried over Na2SO4
filtrationfiltered
concentrationthe filtrate was concentrated under reduced pressure
customPurification of the residue
washby flash chromatography (SiO2, 20 to 30% EtOAc/Hex, gradient elution)

Sources & evidence

ORD record: ord-e57188db23e24bbfbf3ec2534715c02d
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569341B2

Reaction notes

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