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

HRID 74616Notes

Reaction equation

HRID 74616 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>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

5

Reactant 2

HCID 21225700Diisobutylaluminumhydride2×HCID 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 di-isobutyl-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 stirred for 20 h at RT. Then the reaction mixture was refluxed for 8 h. A 1M diisobutylaluminium hydride solution in toluene was added twice more and the mixture was refluxed for 8 h and 24 h in each case. 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 in each case
  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-0fc481b970a945f3b82122cf544fecbd
Source dataset
uspto-grants-2014_09
Patent number
US08829006B2

Reaction notes

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