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

HRID 932298Notes

Reaction equation

HRID 932298 reaction equation
CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].[CH2:15]([C@@:18]1([CH3:45])[CH2:23][C@H:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=2)[C@@H:21]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=2)[N:20]([C@@H:38]([CH2:42][CH3:43])[C:39](=[O:41])[CH3:40])[C:19]1=[O:44])[CH:16]=[CH2:17]>C1COCC1>[CH2:15]([C@@:18]1([CH3:45])[CH2:23][C@H:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=2)[C@@H:21]([C:31]2[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=2)[N:20]([C@@H:38]([CH2:42][CH3:43])[C@@H:39]([OH:41])[CH3:40])[C:19]1=[O:44])[CH:16]=[CH2:17]

Participants

4

Reactant 2

HCID 3611392Lithium tri-s-butylborohydrideHCID 58573535(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-2-oxopentan-3-yl)piperidin-2-one

Product 1

HCID 58573194(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-e3ccf146cbd045928f2c100138218038
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

Loading…