Benzene, 1-bromo-4-(trifluoromethyl)- → HCID 68071226, compound

HRID 2200079Notes

Reaction equation

HRID 2200079 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].Br[C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=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:15])[NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 634876Binap, (A+-)-HCID 2756030tert-butyl N-[(piperidin-3-yl)methyl]carbamateHCID 23676156Sodium t-butoxide

Product 1

HCID 68071226HCID 68071226, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of piperidin-3-ylmethyl-carbamic acid tert-butyl ester (1.00 g, 4.67 mmol), 1-bromo-4-trifluoromethyl-benzene (1.15 g, 5.13 mmol), sodium tert-butoxide (673 mg, 7.00 mmol), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (291 mg, 0.47 mmol) and tris(dibenzylideneacetone)-dipalladium (0) (214 mg, 0.23 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. Filtration followed by concentration in vacuo to afford crude [1-(4-trifluoromethyl-phenyl)-piperidin-3-ylmethyl]-carbamic acid tert-butyl ester (1.5 g, 90% crude) 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. filtrationFiltration
  9. concentrationfollowed by concentration in vacuo

Sources & evidence

ORD record
ord-c793dff9769c41bc8e6f4efe7d9d3d5f
Source dataset
uspto-grants-2016_06
Patent number
US09359337B2

Reaction notes

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