Lithium tri-s-butylborohydride → (3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-3-methylpiperidin-2-one

L-Selectride™ (1M in THF, 5.24 ml, 5.24 mmol) was added to a solution at −10° C. of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-2-oxopentan-3-yl)piperidin-2-one (Example 149, step A, 2 g, 4.36 mmol) in THF (29.1 ml) being careful to maintain the temperature below −7° C. The reaction was stirred for 40 min then quenched into an aqueous solution of Oxone™ (10.73 g, 17.45 mmol) in 60 mL water. It was noted that the temperature spiked up to 40° C. during the addition. The reaction was cooled to RT using a water/ice bath and stirred at RT for 1 h, then diluted with ethyl acetate. The layers were separated and the aq layer was extracted with ethyl acetate. The combined organics were washed with brine and dried over MgSO4, filtered and concentrated. The crude material was dried under high vacuum overnight. Purification by column chromatography using 10-20% acetone in hexanes afforded the title compound.

1. temperatureto maintain the temperature below −7° C
2. customthen quenched into an aqueous solution of Oxone™ (10.73 g, 17.45 mmol) in 60 mL water
3. additionspiked up to 40° C. during the addition
4. stirringstirred at RT for 1 h
5. additiondiluted with ethyl acetate
6. customThe layers were separated
7. extractionthe aq layer was extracted with ethyl acetate
8. washThe combined organics were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. dry with materialThe crude material was dried under high vacuum overnight
13. customPurification by column chromatography

ORD-Eintrag

ord-e3ccf146cbd045928f2c100138218038

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09296736B2