Tetrabutylammonium Fluoride → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-3-(2-hydroxyethyl)-3-(2-(pyrrolidin-1-yl)ethyl)piperidin-2-one

HRID 1048272Notes

Reaction equation

HRID 1048272 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:11](=[O:25])[C:10]([CH2:39][CH2:40][N:41]3[CH2:45][CH2:44][CH2:43][CH2:42]3)([CH2:26][CH2:27][O:28][Si](C(C)C)(C(C)C)C(C)C)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH2:21][CH:22]3[CH2:23][CH2:24]3)[C:11](=[O:25])[C:10]([CH2:26][CH2:27][OH:28])([CH2:39][CH2:40][N:41]3[CH2:45][CH2:44][CH2:43][CH2:42]3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 58573643(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-3-(2-(pyrrolidin-1-yl)ethyl)-3-(2-(triisopropylsilyloxy)ethyl)piperidin-2-one

Product 1

HCID 58573627(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-3-(2-hydroxyethyl)-3-(2-(pyrrolidin-1-yl)ethyl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cooled solution of 1.12 g (1.66 mmol) of crude (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-3-(2-(pyrrolidin-1-yl)ethyl)-3-(2-(triisopropylsilyloxy)ethyl)piperidin-2-one (Example 69, Step C, mixture of diastereomers) in THF (55 mL) added 8.3 mL (8.3 mmol) of a 1M solution of TBAF in THF. After being stirred at room temperature for 1.5 h, the reaction mixture was quenched with water and extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), and concentrated under the reduced pressure. Purification of the residue by flash chromatography on silica gel (3-30% MeOH/DCM, gradient elution) provided the title compound (mixture of C-3 epimers) as a light yellow oil.

Workup

  1. customthe reaction mixture was quenched with water
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated under the reduced pressure
  5. customPurification of the residue by flash chromatography on silica gel (3-30% MeOH/DCM, gradient elution)

Sources & evidence

ORD record
ord-fd8818bdefbe4603a56923572eb15c8f
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

Loading…