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

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.

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

ORD record

ord-b89b24fb753543b28086f5ca2cd9ef30

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569341B2