Dibah → (S)-2-(3,5-difluorophenyl)-5,5-dimethylpiperidine

HRID 1640264Notes

Reaction equation

HRID 1640264 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[F:11][C:12]1[CH:13]=[C:14]([C@H:19]2[NH:24][C:23](=O)[C:22]([CH3:27])([CH3:26])[CH2:21][CH2:20]2)[CH:15]=[C:16]([F:18])[CH:17]=1.C([Al]CC(C)C)C(C)C>C1(C)C=CC=CC=1.C1COCC1>[F:18][C:16]1[CH:15]=[C:14]([C@@H:19]2[CH2:20][CH2:21][C:22]([CH3:27])([CH3:26])[CH2:23][NH:24]2)[CH:13]=[C:12]([F:11])[CH:17]=1

Participants

6

Reactant 3

HCID 16682954DibahHCID 21225700DiisobutylaluminumhydrideHCID 57974061HCID 57974061, compound

Product 1

HCID 66722231(S)-2-(3,5-difluorophenyl)-5,5-dimethylpiperidine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

7.0 mL (7.0 mmol) of a 1 molar diisobutyl-aluminium hydride solution in toluene were added to 0.48 g (2.0 mmol) (S)-6-(3,5-difluorophenyl)-3,3-dimethylpiperidin-2-one in 10 mL THF while cooling with ice and the mixture was stirred for 20 h at RT. Then the reaction mixture was refluxed for 8 h. A 1 M diisobutylaluminium hdyride solution in toluene was added twice more and the mixture was refluxed for 8 h and 24 h, respectively. After hydrolysis of the reaction mixture the precipitate formed was suction filtered and washed with THF. The filtrate was evaporated down and the residue was purified by flash chromatography (aluminium oxide).

Workup

  1. temperaturewhile cooling with ice
  2. temperatureThen the reaction mixture was refluxed for 8 h
  3. temperaturethe mixture was refluxed for 8 h and 24 h
  4. customAfter hydrolysis of the reaction mixture the precipitate
  5. customformed
  6. filtrationfiltered
  7. washwashed with THF
  8. customThe filtrate was evaporated down
  9. customthe residue was purified by flash chromatography (aluminium oxide)

Sources & evidence

ORD record
ord-113a9ea1b16944ec8256c58241b51771
Source dataset
uspto-grants-2012_02
Patent number
US08110575B2

Reaction notes

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