Toluene → HCID 44573418, compound

HRID 737074Notes

Reaction equation

HRID 737074 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][O:10][C@@H: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([C@@H: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 57849488HCID 57849488, compound

Product 1

HCID 44573418HCID 44573418, compoundYield 69.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

106 mg of (S)-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-1be921f0c2c045208c92f526ce93c686
Source dataset
uspto-grants-2009_09
Patent number
US07595397B2

Reaction notes

Loading…