Toluene → 2-Phenyl-4-(2'-trifluoromethyl-biphenyl-4-ylmethyl)-morpholine

HRID 737069Notes

Reaction equation

HRID 737069 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][O:10][CH:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:8]2)=[CH:4][CH:3]=1.[F:21][C:22]([F:33])([F:32])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[C:13]1([CH:9]2[O:10][CH2:11][CH2:12][N:7]([CH2:6][C:5]3[CH:19]=[CH:20][C:2]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=4[C:22]([F:33])([F:32])[F:21])=[CH:3][CH:4]=3)[CH2:8]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 578495044-(4-Bromo-benzyl)-2-phenyl morpholine

Product 1

HCID 161268492-Phenyl-4-(2'-trifluoromethyl-biphenyl-4-ylmethyl)-morpholineYield 69.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

106 mg of 4-(4-Bromo-benzyl)-2-phenyl-morpholine was combined with 91 mg of 2-(Trifluoromethyl)phenyl boronic acid, 18 mg of tetrakis(triphenylphosphine)palladium(0), 1.1 mL of 2M sodium carbonate solution, 2.9 mL toluene and 1.4 mL ethanol. The reaction mixture was heated in a sealed tube at 120° C. overnight in an oil bath. The reaction mixture was filtered through Celite and concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by flash chromatography eluting in a 10 to 40% ethyl acetate/hexanes gradient. The product fractions were pooled and concentrated to afford 88.3 mg of product. ES MS (+) m/z 398

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash chromatography
  10. washeluting in a 10 to 40% ethyl acetate/hexanes gradient
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e1de05e62a414082b5fe2c464728be32
Source dataset
uspto-grants-2009_09
Patent number
US07595397B2

Reaction notes

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