Potassium Carbonate → Tert-butyl(trans)-2-(3'-(trifluoromethyl)biphenyl-4-yl)cyclopropylcarbamate

HRID 1470550

Reaction equation

HRID 1470550 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:25][C:26]([F:37])([F:36])[C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1>C(#N)C.O>[F:25][C:26]([F:37])([F:36])[C:27]1[CH:32]=[C:31]([C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[CH2:10][C@H:9]3[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=2)[CH:30]=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 86658779tert-butyl ((1R,2S)-2-(4-bromophenyl)cyclopropyl)carbamate

Product 1

HCID 86673371Tert-butyl(trans)-2-(3'-(trifluoromethyl)biphenyl-4-yl)cyclopropylcarbamateYield 66.2%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a solution of tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate (Intermediate E[a2]) (1 g, 3.2 mmol), potassium carbonate (1.31 g, 9.6 mmol), 3-(trifluoromethyl) phenylboronic acid (0.73 g, 3.8 mmol) in acetonitrile:water (4:1) were degassed for 30 mins, added tetrakis triphenylphosphine palladium (36 mg, 0.032 mmol), degassed again for 10 mins, heated the reaction mixture at reflux temperature for 5 h. After completion, the reaction mixture was poured in ice water (50 mL), extracted with, ethyl acetate (2×50 mL). Combined extracts were washed with water (70 mL), brine (70 mL), dried over anhydrous Na2SO4, filtered and evaporated. The crude residue was purified by column chromatography (SiO2), by using EtOAc:Petroleum ether (2:8) to get tert-butyl (trans)-2-(3′-(trifluoromethyl)biphenyl-4-yl)cyclopropylcarbamate (0.8 g, 66%) as a white solid.

Workup

  1. customdegassed again for 10 mins
  2. temperatureheated the reaction mixture
  3. temperatureat reflux temperature for 5 h
  4. additionAfter completion, the reaction mixture was poured in ice water (50 mL)
  5. extractionextracted with, ethyl acetate (2×50 mL)
  6. washCombined extracts were washed with water (70 mL), brine (70 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude residue was purified by column chromatography (SiO2)

Sources & evidence

ORD record
ord-9ff134d1486d41a2a690bc1caa39c725
Source dataset
uspto-grants-2015_04
Patent number
US09006449B2

Linked notes

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