Hydrochloric Acid → 4-Pentyl(2,3-difluorophenyl)cyclohexanol

HRID 1943542Notes

Reaction equation

HRID 1943542 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[F:8].C([Li])(CC)C.[CH2:14]([CH:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)[CH2:15][CH2:16][CH2:17][CH3:18].Cl>C(OCC)(=O)C.C1COCC1.C1CCCCC1.CCCCCC>[CH2:14]([CH:19]1[CH2:20][CH2:21][C:22]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=2[F:8])([OH:25])[CH2:23][CH2:24]1)[CH2:15][CH2:16][CH2:17][CH3:18]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 97061,2-DifluorobenzeneHCID 5660974-PentylcyclohexanoneHCID 178418400CID 53628100

Product 1

HCID 596098104-Pentyl(2,3-difluorophenyl)cyclohexanolYield 86.9%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,2-Difluorobenzene (6) (100.0 g) and THF (500 ml) were put in a reaction vessel under a nitrogen atmosphere, and cooled to −74° C. sec-Butyllithium (1.00 M, in a n-hexane and cyclohexane solution; 876.5 ml) was added dropwise thereto in the temperature range of −74° C. to −70° C., and the mixture was stirred for another 2 hours. Then, 4-pentylcyclohexanone (7) (177.0 g) in a THF (200 ml) solution was added dropwise thereto in the temperature range of −75° C. to −70° C., and the stirring was continued for another 8 hours while the mixture was allowed to return to 25° C. The reaction mixture obtained was poured into a vessel containing an aqueous 1N-HCl solution (500 ml) and ethyl acetate (500 ml), and mixed. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases, and extraction was carried out. The organic phase obtained was fractionated, washed sequentially with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, giving 215.1 g of 4-pentyl(2,3-difluorophenyl)cyclohexanol (8). The compound (8) obtained was a yellow oil.

Workup

  1. addition876.5 ml) was added dropwise
  2. waitin the temperature range of −75° C. to −70° C., and the stirring was continued for another 8 hours while the mixture
  3. customto return to 25° C
  4. customThe reaction mixture obtained
  5. additionwas poured into a vessel
  6. additionmixed
  7. customhad separated into two phases of organic and
  8. extractionaqueous phases, and extraction
  9. customThe organic phase obtained
  10. washwashed sequentially with water
  11. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate
  12. distillationThe solvent was then distilled off under reduced pressure

Sources & evidence

ORD record
ord-2e3a1d3de6a24d70a918a5b768d99965
Source dataset
uspto-grants-2013_03
Patent number
US08394294B2

Reaction notes

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