Benzene, 1-bromo-4-(trifluoromethyl)- → HCID 90165962, compound

HRID 2200081Notes

Reaction equation

HRID 2200081 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH:3]([CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:2]1.Br[C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[C:11]([O:10][C:9](=[O:15])[NH:8][CH2:7][CH:3]1[O:4][CH2:5][CH2:6][N:1]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[CH2:2]1)([CH3:12])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 19081107tert-Butyl [(morpholin-2-yl)methyl]carbamateHCID 23676156Sodium t-butoxide

Product 1

HCID 90165962HCID 90165962, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

tert-Butyl morpholin-2-ylmethylcarbamate (1.0 g, 4.62 mmol), 1-bromo-4-(trifluoromethyl)benzene (1.04 g, 4.62 mmol), Pd(dba)2 (133 mg, 0.23 mmol), X-Phos (220 mg, 0.46 mmol) and sodium tert-butoxide (533 mg, 5.55 mol) were combined in 10 mL of dry toluene in a sealed tube. The mixture was degassed with argon and then stirred at 105° C. for 4 h. The mixture was filtered through a layer of Celite and rinsed with THF. Solvents were evaporated and the residue was extracted with water and ethyl acetate. The organic layer was dried and concentrated. The residue was purified by ISCO flash column chromatography (50 g silica gel, ethyl acetate in hexanes 0% to 80%) to give the desired compound (727 mg, 44%).

Workup

  1. customThe mixture was degassed with argon
  2. filtrationThe mixture was filtered through a layer of Celite
  3. washrinsed with THF
  4. customSolvents were evaporated
  5. extractionthe residue was extracted with water and ethyl acetate
  6. customThe organic layer was dried
  7. concentrationconcentrated
  8. customThe residue was purified by ISCO flash column chromatography (50 g silica gel, ethyl acetate in hexanes 0% to 80%)

Sources & evidence

ORD record
ord-96e48b7489904d7f833d72793f12b408
Source dataset
uspto-grants-2016_06
Patent number
US09359337B2

Reaction notes

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