Water → 2-{(2R)-2-(3,4-dichlorophenyl)-4-[3,5-bis(trifluoromethyl)benzoyl]morpholin-2-yl}ethanol

HRID 901979Notes

Reaction equation

HRID 901979 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH2:15][CH2:16][OH:17])[O:14][CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(N(CC)CC)C.[F:25][C:26]([F:41])([F:40])[C:27]1[CH:28]=[C:29]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[C:30](Cl)=[O:31].O>C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH2:15][CH2:16][OH:17])[O:14][CH2:13][CH2:12][N:11]([C:30](=[O:31])[C:29]3[CH:33]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:35]=[C:27]([C:26]([F:25])([F:40])[F:41])[CH:28]=3)[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 10956756(2R)-2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol

Product 1

HCID 865997912-{(2R)-2-(3,4-dichlorophenyl)-4-[3,5-bis(trifluoromethyl)benzoyl]morpholin-2-yl}ethanolYield 54.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

5.60 g (20.3 mmol) of 2-[(2R)-2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol (specification of U.S. Pat. No. 6,159,967, EXAMPLE 51(d)) was dissolved in methylene chloride (60 mL) and 2.83 mL (24.3 mmol) of triethylamine was added thereto. 5.60 g (20.3 mmol) of 3,5-bis(trifluoromethyl)benzoyl chloride and 248 mg (2.03 mmol) of 4-dimethylaminopyridine were added to the mixture under ice-cooling and the mixture was stirred at room temperature for 2 hours under a nitrogen atmosphere. Water was added to the reaction mixture and the methylene chloride layer was washed with water and a saturated NaCl solution and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate=1/1) to obtain 5.68 g (yield: 54%) of 2-{(2R)-2-(3,4-dichlorophenyl)-4-[3,5-bis(trifluoromethyl)benzoyl]morpholin-2-yl}ethanol.

Workup

  1. temperaturecooling
  2. washthe methylene chloride layer was washed with water
  3. dry with materiala saturated NaCl solution and dried over anhydrous magnesium sulfate
  4. filtrationAfter filtration
  5. distillationthe solvent was distilled off under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (eluting solvent: hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-b517331a31bc4e709448db23dc9e809a
Source dataset
uspto-grants-2008_04
Patent number
US07365067B2

Reaction notes

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