Water → (S)-2-((3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal

HRID 932100Notes

Reaction equation

HRID 932100 reaction equation
[CH2:1]([C@@:4]1([CH3:30])[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]([CH2:27][CH3:28])[CH2:25][OH:26])[C:5]1=[O:29])[CH:2]=[CH2:3].O.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(OCC)C>ClCCl>[CH2:1]([C@@:4]1([CH3:30])[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]([CH2:27][CH3:28])[CH:25]=[O:26])[C:5]1=[O:29])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 962WaterHCID 3283Diethyl EtherHCID 159087TriacetoxyperiodinaneHCID 58573282(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one

Product 1

HCID 58573909(S)-2-((3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 428 g (959 mmol) of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 151, Step A) in dichloromethane (4.55 L) was added 25.9 mL (1.44 mol) of water. A solution of 610 g (1.44 mol) of Dess-Martin periodinane in dichloromethane (4.55 L) was added slowly over a 25 min period so as to maintain an internal reaction temperature not exceeding 25° C. The white slurry was stirred for 2.5 h and then was quenched by cautious, slow addition of saturated aqueous sodium thiosulfate (5.2 L) so as to maintain an internal reaction temperature below 30° C. Water was added and the mixture was extracted with dichloromethane (3×). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (4×) and then saturated aqueous sodium chloride (1×), dried over Na2SO4, filtered and the filtrate was concentrated to afford a yellow oily solid. A mixture of ethyl ether and DCM were added, and precipitated solids were filtered off. The precipitation/filtration process was repeated. The filtrate was concentrated to provide the title compound as a white solid. The crude product was used directly in the next step.

Workup

  1. temperatureto maintain an internal reaction temperature not
  2. customexceeding 25° C
  3. customwas quenched by cautious,
  4. additionslow addition of saturated aqueous sodium thiosulfate (5.2 L) so as
  5. temperatureto maintain an internal reaction temperature below 30° C
  6. additionWater was added
  7. extractionthe mixture was extracted with dichloromethane (3×)
  8. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution (4×)
  9. dry with materialsaturated aqueous sodium chloride (1×), dried over Na2SO4
  10. filtrationfiltered
  11. concentrationthe filtrate was concentrated
  12. customto afford a yellow oily solid
  13. additionwere added
  14. customprecipitated solids
  15. filtrationwere filtered off
  16. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-fa3bfbdc2df14eada034145dbcd00b9b
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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