Water → HCID 178448055, compound

HRID 1264462Notes

Reaction equation

HRID 1264462 reaction equation
[CH2:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C@H:10]2[CH2:15][CH2:14][C@H:13]([CH2:16][CH2:17][C:18]([OH:20])=[O:19])[CH2:12][CH2:11]2)[CH2:6][CH2:5]1)[CH2:2][CH3:3].[F:21][C:22]1[C:27]([F:28])=[C:26]([O:29][CH2:30][CH3:31])[CH:25]=[CH:24][C:23]=1O.C1(N=C=NC2CCCCC2)CCCCC1.O>ClCCl.CN(C)C1C=CN=CC=1>[CH2:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C@H:10]2[CH2:15][CH2:14][C@H:13]([CH2:16][CH2:17][C:18]([O:20][C:23]3[CH:24]=[CH:25][C:26]([O:29][CH2:30][CH3:31])=[C:27]([F:28])[C:22]=3[F:21])=[O:19])[CH2:12][CH2:11]2)[CH2:6][CH2:5]1)[CH2:2][CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 10868DicyclohexylcarbodiimideHCID 144957634-Ethoxy-2,3-difluorophenolHCID 178448056HCID 178448056, compound

Product 1

HCID 178448055HCID 178448055, compoundYield 102.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

In a 3-L three-neck flask equipped with a stirrer, a thermometer and a dropping funnel, 32.0 g (114.9 mmol) of 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propionic acid and 20.0 g (114.9 mmol) of 2,3-difluoro-4-ethoxyphenol were dissolved in 1000 ml of dichloromethane at room temperature under nitrogen atmosphere, and 15.4 g (126.4 mmol) of 4-dimethylaminopyridine was added thereto. The solution was stirred for 30 minutes thereafter, and then 26.1 g (126.4 mmol) of dicyclohexylcarbodiimide was dissolved in 400 ml of dichloromethane to prepare a solution, which was added dropwise to the reaction mixture at room temperature. After dropwise adding, the solution was stirred at room temperature for 14 hours. 500 ml of water was added to the reaction solution, insoluble materials were filtered, and then the filtrate was washed with 300 ml of 3M hydrochloric acid, 300 ml of water, 300 ml of a saturated aqueous sodium hydrogencarbonate solution and 600 ml of water and dried over anhydrous magnesium sulfate. The solvent was distilled off from the reaction solution under reduce pressure to obtain 56.4 g of a concentrated substance, which was then purified by means of a silica gel column chromatography with a mixed solvent of heptane/ethyl acetate (7/3) used as a developing solvent to obtain 51.4 g of 2,3-difluoro-4-ethoxyphenyl 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propionate as colorless crystals.

Workup

  1. customIn a 3-L three-neck flask equipped with a stirrer
  2. customto prepare a solution, which
  3. additionwas added dropwise to the reaction mixture at room temperature
  4. additionAfter dropwise adding
  5. stirringthe solution was stirred at room temperature for 14 hours
  6. filtrationwere filtered
  7. washthe filtrate was washed with 300 ml of 3M hydrochloric acid, 300 ml of water, 300 ml of a saturated aqueous sodium hydrogencarbonate solution and 600 ml of water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off from the reaction solution
  10. customto obtain 56.4 g of a concentrated substance, which
  11. customwas then purified by means of a silica gel column chromatography with a mixed solvent of heptane/ethyl acetate (7/3)

Sources & evidence

ORD record
ord-64a60e954ead4717abe35212f6b37c06
Source dataset
uspto-grants-2003_04
Patent number
US06544604B2

Reaction notes

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