Benzene, 2-bromo-1-chloro-4-methyl- → 4-(2'-Chloro-5'-methyl-biphenyl-4-ylmethyl)-2-phenyl-morpholine

HRID 737076Notes

Reaction equation

HRID 737076 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.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C(=O)(O)[O-].[Na+].Br[C:50]1[CH:51]=[C:52]([CH3:57])[CH:53]=[CH:54][C:55]=1[Cl:56]>CN(C=O)C.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>[Cl:56][C:55]1[CH:54]=[CH:53][C:52]([CH3:57])=[CH:51][C:50]=1[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

Participants

8

Reactant 5

HCID 284147Benzene, 2-bromo-1-chloro-4-methyl-HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 578495044-(4-Bromo-benzyl)-2-phenyl morpholine

Product 1

HCID 235850594-(2'-Chloro-5'-methyl-biphenyl-4-ylmethyl)-2-phenyl-morpholineYield 2.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
120 °C

Procedure

109 mg of 4-(4-Bromo-benzyl)-2-phenyl-morpholine was combined with 102 mg of bis(pinacolato)diboron, 97 mg of potassium acetate, 11 mg tetrakis(triphenylphosphine)palladium(0), and 1.9 mL DMF. The mixture was heated in a microwave reactor at 120° C. for 7 minutes and cooled. 0.8 mL of 2M aqueous sodium bicarbonate was added along with 101 mg of 3-Bromo-4-chlorotoluene in 0.15 mL DMF. The mixture was heated in the microwave reactor for an additional 5 minutes at 120° C. The reaction was cooled and filtered through Celite, washing with methylene chloride. The eluant was concentrated and purified by flash chromatography twice using an ethyl acetate/hexanes gradient to afford 3.5 mg of product. ES MS (+) m/z 378

Workup

  1. temperaturecooled
  2. temperatureThe mixture was heated in the microwave reactor for an additional 5 minutes at 120° C
  3. temperatureThe reaction was cooled
  4. filtrationfiltered through Celite
  5. washwashing with methylene chloride
  6. concentrationThe eluant was concentrated
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-c0d09dd52183439b82398053a9565d91
Source dataset
uspto-grants-2009_09
Patent number
US07595397B2

Reaction notes

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