Tetrabutylammonium Fluoride → (3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one

HRID 932269Notes

Reaction equation

HRID 932269 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[CH2:19]([C@:22]1([CH2:65][O:66][CH2:67][CH2:68][Si:69]([CH3:72])([CH3:71])[CH3:70])[CH2:27][C@H:26]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)[C@@H:25]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)[N:24]([C@@H:42]([CH2:62][CH3:63])[CH2:43][O:44][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[C:23]1=[O:64])[CH:20]=[CH2:21]>C1COCC1.CCOC(C)=O>[CH2:19]([C@@:22]1([CH2:65][O:66][CH2:67][CH2:68][Si:69]([CH3:72])([CH3:71])[CH3:70])[CH2:27][C@H:26]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)[C@@H:25]([C:35]2[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=2)[N:24]([C@@H:42]([CH2:62][CH3:63])[CH2:43][OH:44])[C:23]1=[O:64])[CH:20]=[CH2:21]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 68000002(3R,5R,6S)-3-Allyl-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one

Product 1

HCID 58573707(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 1M solution of TBAF in THF (2.15 mL, 2.15 mmol) was added to a solution of (3S,5R,6S)-3-allyl-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2-(trimethylsilyl)ethoxy)methyl)piperidin-2-one (Example 414, Step A; 860 mg, 1.074 mmol) in THF. The reaction was heated to reflux for 3 hours. After cooling, it was diluted with EtOAc and washed with HCl (1N in water). The organic extract was washed with satd NaCl and dried over Na2SO4. The solution was filtered and concentrated to give the crude material as a glass which was purified by chromatography on silica eluting with 20% EtOAc in hexane, to provide the title compound as a solid.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 3 hours
  3. temperatureAfter cooling
  4. washwashed with HCl (1N in water)
  5. extractionThe organic extract
  6. washwas washed with satd NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationThe solution was filtered
  9. concentrationconcentrated
  10. customto give the crude material as a glass which
  11. customwas purified by chromatography on silica eluting with 20% EtOAc in hexane

Sources & evidence

ORD record
ord-a56ba6981734495eaaa93ae6397a1ed0
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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