Hydrochloric Acid → 3,3'-Difluoro-4'-(1-hydroxy-4-propylcyclohexyl)-4-propoxybiphenyl

HRID 1530757Notes

Reaction equation

HRID 1530757 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH3:11].C([Li])(CC)C.[CH2:24]([CH:27]1[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]1)[CH2:25][CH3:26].Cl>C1COCC1.CCCCCCC.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([C:30]3([OH:33])[CH2:31][CH2:32][CH:27]([CH2:24][CH2:25][CH3:26])[CH2:28][CH2:29]3)=[C:14]([F:18])[CH:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH3:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1424824-PropylcyclohexanoneHCID 212524043,3'-Difluoro-4-propoxybiphenylHCID 178418400CID 53628100

Product 1

HCID 212523993,3'-Difluoro-4'-(1-hydroxy-4-propylcyclohexyl)-4-propoxybiphenylYield 90.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
-60 °C

Procedure

To a solution of 15.0 g (60.4 mmol) of the 3,3′-difluoro-4-propoxybiphenyl obtained in the first step of Example 1 in 85 ml of THF was added by drops 70 ml (1.04M, cyclohexane solution, corresponding to 72.5 mmol) of sec-butyllithium while being maintained at a temperature lower than −60° C. After finishing of the dropping, it was stirred at the same temperature for 1 hour. Subsequently, a solution of 11.0 g (78.5 mmol) of 4-propylcyclohexanone in 55 ml of THF was added by drops thereto while being maintained at a temperature of −60° C., stirred at the same temperature for 3 hours, and then further stirred at room temperature for 2 hours. After 200 ml of a diluted hydrochloric acid was added by drops to the reaction liquid, it was extracted with 200 ml of toluene. The organic layer thus obtained was washed with a diluted aqueous sodium bicarbonate solution twice and with water thrice, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under a reduced pressure, and the residue thus obtained was subjected to silica gel column chromatography (eluent: heptane/ethyl acetate=8/2) to obtain 21.2 g of a crude 3,3′-difluoro-4′-(1-hydroxy-4-propylcyclohexyl)-4-propoxybiphenyl. (Yield: 90.6%)

Workup

  1. temperaturewhile being maintained at a temperature of −60° C.
  2. stirringstirred at the same temperature for 3 hours
  3. stirringfurther stirred at room temperature for 2 hours
  4. extractionwas extracted with 200 ml of toluene
  5. customThe organic layer thus obtained
  6. washwas washed with a diluted aqueous sodium bicarbonate solution twice
  7. dry with materialwith water thrice, and then dried over anhydrous magnesium sulfate
  8. distillationThe solvent was distilled off under a reduced pressure
  9. customthe residue thus obtained

Sources & evidence

ORD record
ord-4dea5cce69184bf1ba473b72427d089a
Source dataset
uspto-grants-2001_03
Patent number
US06197217B1

Reaction notes

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