Acetonitrile → 5-[4-(4-Ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyran

HRID 605454Notes

Reaction equation

HRID 605454 reaction equation
ClCCl.C(#N)C.[CH2:7]([O:9][C:10]1[CH:33]=[CH:32][C:13]([O:14][CH2:15][CH:16]2[CH2:21][CH2:20][CH:19]([CH:22]3[CH2:27][O:26][C:25]([CH2:29][CH2:30][CH3:31])(O)[CH2:24][CH2:23]3)[CH2:18][CH2:17]2)=[C:12]([F:34])[C:11]=1[F:35])[CH3:8].C([SiH](CC)CC)C>O>[CH2:7]([O:9][C:10]1[CH:33]=[CH:32][C:13]([O:14][CH2:15][CH:16]2[CH2:17][CH2:18][CH:19]([CH:22]3[CH2:27][O:26][CH:25]([CH2:29][CH2:30][CH3:31])[CH2:24][CH2:23]3)[CH2:20][CH2:21]2)=[C:12]([F:34])[C:11]=1[F:35])[CH3:8]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 6344DichloromethaneHCID 12052TriethylsilaneHCID 668770885-[4-(4-Ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyran-2-ol

Product 1

HCID 536308445-[4-(4-Ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyranYield 57.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a reactor under nitrogen atmosphere, 100 mL of dichloromethane and 20 mL of acetonitrile were added to 3.6 g of 5-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyran-2-ol obtained in the thirteenth step, and the mixture was cooled to −20° C., to which 2.7 mL of triethylsilane was added dropwise, and subsequently 1.5 mL of boron trifluoride diethyl ether complex was added dropwise. The temperature of the reaction solution was increased to 0° C., to which 50 mL of iced water was added, followed by extracting three times with 30 mL of diethyl ether. The mixture including the organic layer was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography and recrystallization to provide 2.0 g of 5-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyran.

Workup

  1. customobtained in the thirteenth step
  2. additionwas added dropwise
  3. additionsubsequently 1.5 mL of boron trifluoride diethyl ether complex was added dropwise
  4. additionwas added
  5. extractionby extracting three times with 30 mL of diethyl ether
  6. washwas washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was purified by silica gel column chromatography and recrystallization

Sources & evidence

ORD record
ord-8d0d76c7ac204acda5a3922bca895019
Source dataset
uspto-grants-2011_03
Patent number
US07914862B2

Reaction notes

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