Benzene, 1-bromo-4-(trifluoromethyl)- → HCID 90165960, compound

HRID 2200080Notes

Reaction equation

HRID 2200080 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH2:8][CH:9]1[CH2:13][CH2:12][NH:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].Br[C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6](=[O:14])[NH:7][CH2:8][CH:9]1[CH2:13][CH2:12][N:11]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 634876Binap, (A+-)-HCID 4250767tert-butyl N-((pyrrolidin-3-yl)methyl)carbamateHCID 23676156Sodium t-butoxide

Product 1

HCID 90165960HCID 90165960, compoundYield 58.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of pyrrolidin-3-ylmethyl-carbamic acid tert-butyl ester (0.50 g, 2.50 mmol), 1-bromo-4-trifluoromethyl-benzene (0.62 g, 2.75 mmol), sodium tert-butoxide (0.36 g, 3.47 mmol), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (155 mg, 0.25 mmol) and tris(dibenzylideneacetone)-dipalladium (0) (114 mg, 0.13 mmol) in toluene (5 mL) at 25° C. was purged with nitrogen gas and evacuated three times. The solution was sealed and heated to 120° C. for 14 h. The reaction mixture was cooled to 25° C., unsealed and poured into water. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. Solvents were evaporated and the residue was purified by flash column chromatography (80/20 hexanes/ethyl acetate) to afford [1-(4-trifluoromethyl-phenyl)-pyrrolidin-3-ylmethyl]-carbamic acid tert-butyl ester (500 mg, 58%) as a light oil.

Workup

  1. customevacuated three times
  2. customThe solution was sealed
  3. temperatureThe reaction mixture was cooled to 25° C.
  4. additionunsealed and poured into water
  5. extractionThe aqueous phase was extracted three times with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. customSolvents were evaporated
  9. customthe residue was purified by flash column chromatography (80/20 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-65cfc45b6c154fa1b88ca824e671b95c
Source dataset
uspto-grants-2016_06
Patent number
US09359337B2

Reaction notes

Loading…