1,2-Difluorobenzene → HCID 58212299, compound

HRID 1095252Notes

Reaction equation

HRID 1095252 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:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1)[CH2:15][CH3:16].[Cl-].[NH4+]>C1(C)C=CC=CC=1.C1COCC1.C1CCCCC1.CCCCCC>[F:1][C:2]1[C:3]([F:8])=[CH:4][CH:5]=[CH:6][C:7]=1[C:20]1([OH:23])[CH2:21][CH2:22][CH:17]([CH2:14][CH2:15][CH3:16])[CH2:18][CH2:19]1

Participants

9

Reactant 4

HCID 97061,2-DifluorobenzeneHCID 25517Ammonium ChlorideHCID 1424824-PropylcyclohexanoneHCID 178418400CID 53628100

Product 1

HCID 58212299HCID 58212299, compoundYield 91.3%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8078CyclohexaneSolvent

Procedure

1,2-Difluorobenzene (29) (58.8 g) and THF (500 ml) were put in a reaction vessel under a nitrogen atmosphere, and cooled to −73° C. s-Butyllithium (1.03 M, in a n-hexane and cyclohexane solution; 500.0 ml) was added dropwise thereto in the temperature range of −74° C. to −65° C., and the mixture was stirred for another 2 hours. Subsequently, 4-propylcyclohexanone (30) (72.2 g) in a THF (200 ml) solution was added dropwise thereto in the temperature range of −76° C. to −65° C., and the stirring was continued for another 20 hours while the mixture was allowed to return to 25° C. Then, the reaction mixture was poured into a vessel containing ammonium chloride (55.1 g) and ice-water (1,000 ml), and mixed. Toluene (1500 ml) was added thereto and the mixture was allowed to separate into organic and aqueous phases, and then an extractive operation was carried out. The organic phase was fractionated, and washed sequentially with water and a saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, giving 119.6 g of 1-(2,3-difluorophenyl)-4-propylcyclohexanol (31). The compound (31) was yellow oil.

Workup

  1. addition500.0 ml) was added dropwise
  2. waitin the temperature range of −76° C. to −65° C., and the stirring was continued for another 20 hours while the mixture
  3. customto return to 25° C
  4. additionThen, the reaction mixture was poured into a vessel
  5. additionmixed
  6. customto separate into organic and aqueous phases
  7. washwashed sequentially with water
  8. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-dfcb7919ff8f4e9288bad51404cdd64e
Source dataset
uspto-grants-2012_03
Patent number
US08137583B2

Reaction notes

Loading…