Tetrabutylammonium Fluoride → (5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one

HRID 932053Notes

Reaction equation

HRID 932053 reaction equation
[CH2:1]([C:4]1([CH3:47])[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][N:18]=2)[N:6]([C@@H:24]([CH2:44][CH3:45])[CH2:25][O:26][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[C:5]1=[O:46])[CH:2]=[CH2:3].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH2:1]([C:4]1([CH3:47])[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][N:18]=2)[N:6]([C@@H:24]([CH2:44][CH3:45])[CH2:25][OH:26])[C:5]1=[O:46])[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67998884(5R,6S)-3-allyl-1-((S)-1-((tert-butyldiphenylsilyl)oxy)butan-2-yl)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-3-methylpiperidin-2-one

Product 1

HCID 58573550(5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cooled solution of 1.30 g (1.90 mmol) of(5R,6S)-3-allyl-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-3-methylpiperidin-2-one (Example 121, Step K) in THF (55 mL) was added 11.37 mL (11.37 mmol) of a 1 M solution of TBAF in THF. The orange solution was warmed to room temperature and stirred for 3.75 h. The reaction was partitioned between 1 M HCl and EtOAc (2×), and then the combined organic layers were washed with water (2×). The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (0 to 10% MeOH/DCM, gradient elution) provided the title compound as a light yellow solid.

Workup

  1. customThe reaction was partitioned between 1 M HCl and EtOAc (2×)
  2. washthe combined organic layers were washed with water (2×)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customPurification of the residue by flash chromatography on silica gel (0 to 10% MeOH/DCM, gradient elution)

Sources & evidence

ORD record
ord-2fa5bd46fc5841f8a4ab26babdbef4c1
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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