3,5-Bis(trifluoromethyl)phenylacetic acid → (2R)-2-[4-{[3,5-bis(trifluoromethyl)phenyl]acetyl}-2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol

HRID 227552

Reaction equation

HRID 227552 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([CH2:13][C:14]([OH:16])=O)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Cl:19][C:20]1[CH:21]=[C:22]([C@@:27]2([CH2:33][CH2:34][OH:35])[O:32][CH2:31][CH2:30][NH:29][CH2:28]2)[CH:23]=[CH:24][C:25]=1[Cl:26]>C(#N)C>[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([CH2:13][C:14]([N:29]2[CH2:30][CH2:31][O:32][C@:27]([CH2:33][CH2:34][OH:35])([C:22]3[CH:23]=[CH:24][C:25]([Cl:26])=[C:20]([Cl:19])[CH:21]=3)[CH2:28]2)=[O:16])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

4

Reactant 2

HCID 1235873,5-Bis(trifluoromethyl)phenylacetic acidHCID 10956756(2R)-2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol

Product 1

HCID 86612947(2R)-2-[4-{[3,5-bis(trifluoromethyl)phenyl]acetyl}-2-(3,4-dichlorophenyl)morpholin-2-yl]ethanolYield 68.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 3,5-bis(trifluoromethyl)phenylacetic acid (10.0 g, 36.8 mmol) in acetonitrile (100 ml), N,N′-carbonyldiimidazole (9.5 g, 58.8 mmol) was added at room temperature, then (2R)-2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol (17.3 g, 62.5 mol) was further added, and the resulting mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was evaporated to dryness. To the obtained residue, methylene chloride (100 ml), water (100 ml) and concentrated hydrochloric acid (15 ml) were added, and the resulting mixture was partitioned. The separated organic layer was washed with water twice (100 ml each) and evaporated to dryness. The residue obtained was purified by chromatography on a silica gel column to afford the title compound [13.3 g, yield: 68.1%] as an oil.

Workup

  1. customAfter completion of the reaction
  2. customthe reaction mixture was evaporated to dryness
  3. additionTo the obtained residue, methylene chloride (100 ml), water (100 ml) and concentrated hydrochloric acid (15 ml) were added
  4. customthe resulting mixture was partitioned
  5. washThe separated organic layer was washed with water twice (100 ml each)
  6. customevaporated to dryness
  7. customThe residue obtained
  8. customwas purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-802b123ba21541afbd5718208b30952e
Source dataset
uspto-grants-2009_07
Patent number
US07560549B2

Linked notes

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