Ammonia → 4'-(4-Butoxy-2,3-difluorophenyl)-bicyclohexanol

HRID 2088247Notes

Reaction equation

HRID 2088247 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([O:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]2[CH2:23][CH2:22][CH:21]([CH:24]3[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)=[C:14]([F:31])[C:13]=1[F:32])[CH2:8][CH2:9][CH3:10].C(OCC)(=[O:35])C.N>C1COCC1>[CH2:7]([O:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]2[CH2:23][CH2:22][CH:21]([C:24]3([OH:35])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)[CH2:20][CH2:19]2)=[C:14]([F:31])[C:13]=1[F:32])[CH2:8][CH2:9][CH3:10]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydrideHCID 666837754'-(4-Butoxy-2,3-difluorophenyl)-bicyclohexyl-4-one

Product 1

HCID 674343264'-(4-Butoxy-2,3-difluorophenyl)-bicyclohexanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminum hydride (0.62 g) was suspended in THF (200 ml). 4′-(4-Butoxy-2,3-difluorophenyl)-bicyclohexyl-4-one (s-7) (10.0 g) was added dropwise to the suspension in the temperature range of −20° C. to −10° C., and the stirring was continued in this temperature range for 2 hours. After the completion of the reaction had been confirmed by means of GC analysis, ethyl acetate and then a saturated aqueous solution of ammonia were added to the reaction mixture under ice-cooling and deposits were removed by filtration through Celite. The filtrate was extracted with ethyl acetate. The combined organic phase was washed successively with water and brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by recrystallization from heptane to give 4′-(4-butoxy-2,3-difluorophenyl)-bicyclohexanol (s-22) (8.8 g). The yield based on the compound (s-7) was 87.5%.

Workup

  1. temperaturecooling
  2. customdeposits were removed by filtration through Celite
  3. extractionThe filtrate was extracted with ethyl acetate
  4. washThe combined organic phase was washed successively with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by recrystallization from heptane

Sources & evidence

ORD record
ord-b609f6659a65442991c113ccc80c9af3
Source dataset
uspto-grants-2013_05
Patent number
US08435422B2

Reaction notes

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