Lithium borohydride → (3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((R)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one

HRID 1048306Notes

Reaction equation

HRID 1048306 reaction equation
[CH2:1]([C@@:4]1([CH3:32])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:29][CH3:30])[C:25](OC)=[O:26])[C:5]1=[O:31])[CH:2]=[CH2:3].[BH4-].[Li+]>CCOCC.C1COCC1>[CH2:1]([C@@:4]1([CH3:32])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[N:6]([C@H:24]([CH2:29][CH3:30])[CH2:25][OH:26])[C:5]1=[O:31])[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 4148881Lithium borohydrideHCID 58573915(S)-Methyl 2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanoate2×

Product 1

HCID 58573492(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((R)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of (S)-methyl 2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanoate and (R)-methyl 2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanoate (1.73 g, 3.64 mmol) (mixture of stereoisomers from Example 91, Step A) in 27 mL of Et2O and 9 mL of THF was added a solution of lithium tetrahydroborate in THF (0.238 mL, 7.28 mmol) at 0° C. The resulting solution was stirred at 25° C. for 2 h. The reaction was quenched (10% citric acid), extracted (2×EtOAc) and washed (1×Sat. aq. NaCl solution). The combined organic layers were washed with sat. aq. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: 0-60% EtOAc in hexanes) to give the title compound as the faster eluting isomer.

Workup

  1. customThe reaction was quenched (10% citric acid)
  2. extractionextracted (2×EtOAc)
  3. washwashed (1×Sat. aq. NaCl solution)
  4. washThe combined organic layers were washed with sat. aq. NaCl solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel (eluent: 0-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3285f19061bb42a8b699a793c6babe3d
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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