Ammonium Chloride → 5-[4-(4-Ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyran-2-ol

HRID 605453Notes

Reaction equation

HRID 605453 reaction equation
[CH2:1]([O:3][C:4]1[CH:24]=[CH:23][C:7]([O:8][CH2:9][CH:10]2[CH2:15][CH2:14][CH:13]([CH:16]3[CH2:21][O:20][C:19](=[O:22])[CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[C:6]([F:25])[C:5]=1[F:26])[CH3:2].[CH2:27]([Li])[CH2:28][CH3:29].[Cl-].[NH4+]>C1COCC1>[CH2:1]([O:3][C:4]1[CH:24]=[CH:23][C:7]([O:8][CH2:9][CH:10]2[CH2:15][CH2:14][CH:13]([CH:16]3[CH2:21][O:20][C:19]([CH2:27][CH2:28][CH3:29])([OH:22])[CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[C:6]([F:25])[C:5]=1[F:26])[CH3:2]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 668767205-[4-(4-Ethoxy2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-oneHCID 178506857HCID 178506857, compound

Product 1

HCID 668770885-[4-(4-Ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyran-2-olYield 872.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

In a reactor under nitrogen atmosphere, 100 mL of THF was added to 4.5 g of 5-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-one obtained in the twelfth step, and the mixture was cooled to −70° C., to which 15 mL of n-propyllithium (about 1.0 mmol) was added dropwise. After stirring the mixture at −70° C. for 1 hour, the temperature of the reaction mixture was increased to room temperature, and 50 mL of a saturated ammonium chloride aqueous solution was added thereto, followed by separating. The aqueous layer was extracted three times with 30 mL of diethyl ether, and the mixture including the organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by distilling off the solvent under reduced pressure. The residue was purified by silica gel column chromatography to provide 3.6 g of 5-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyran-2-ol.

Workup

  1. customobtained in the twelfth step
  2. additionwas added dropwise
  3. temperaturethe temperature of the reaction mixture was increased to room temperature
  4. customby separating
  5. extractionThe aqueous layer was extracted three times with 30 mL of diethyl ether
  6. washwas washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationby distilling off the solvent under reduced pressure
  9. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f3f63f5c1fe44073b0ea0c7706e7b3eb
Source dataset
uspto-grants-2011_03
Patent number
US07914862B2

Reaction notes

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