Tetrabutylammonium Fluoride → Methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-2-oxopiperidin-3-yl)propanoate

HRID 1048381Notes

Reaction equation

HRID 1048381 reaction equation
[Si]([O:18][CH2:19][C@@H:20]([N:23]1[C@H:28]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[C@@H:27]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=2)[CH2:26][C@@H:25]([CH:43]([CH3:48])[C:44]([O:46][CH3:47])=[O:45])[C:24]1=[O:49])[CH2:21][CH3:22])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:42][C:38]1[CH:37]=[C:36]([C@@H:27]2[C@@H:28]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[N:23]([C@@H:20]([CH2:21][CH3:22])[CH2:19][OH:18])[C:24](=[O:49])[C@H:25]([CH:43]([CH3:48])[C:44]([O:46][CH3:47])=[O:45])[CH2:26]2)[CH:41]=[CH:40][CH:39]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67999194Methyl 2-((3S,5R,6S)-1-((S)-1-((tert-butyldiphenylsilyl)oxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl)propanoate

Product 1

HCID 68000935Methyl 2-((3S,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-2-oxopiperidin-3-yl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-((3S,5R,6S)-1-((S)-1-((tert-butyldiphenylsilyl)oxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-3-yl)propanoate (285 mg, 0.398 mmol) (the less polar isomer from step D) in THF (1988 μL) was added TBAF (1.0M in THF) (1590 μL, 1.590 mmol). The mixture was stirred at room temperature for 16 h. The mixture was quenched with 1 M HCl and diluted with EtOAc. The organic layer was washed with sat. aq. NaCl solution, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (11 g VersaPak I-style, Spherical, Supelco, Bellenfonte, Pa.; eluent: 50 to 75% MtBE in hexanes) to give the title compound.

Workup

  1. customThe mixture was quenched with 1 M HCl
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with sat. aq. NaCl solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel (11 g VersaPak I-style, Spherical, Supelco, Bellenfonte, Pa.; eluent: 50 to 75% MtBE in hexanes)

Sources & evidence

ORD record
ord-702bdbd16b0d477ebb8657f1f381e4f7
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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