Boron trifluoride → 1-(2-(Trifluoromethyl)phenyl)cyclopropanamine

HRID 59247Notes

Reaction equation

HRID 59247 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[CH2:13]([Mg]Br)[CH3:14].B(F)(F)F>C(OCC)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:1][C:2]([F:11])([F:12])[C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[C:5]1([NH2:6])[CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 6356Boron trifluorideHCID 679722-(Trifluoromethyl)benzonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 573640411-(2-(Trifluoromethyl)phenyl)cyclopropanamineYield 214.2%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 3283Diethyl EtherSolvent

Procedure

To a cold solution of 2-(trifluoromethyl)benzonitrile (1.0 g, 0.58 mmol) in diethyl ether (20 mL) was added titanium isopropoxide (2.0 g, 0.70 mmol) at −70° C. and ethyl magnesium bromide (4.30 mL, 12.86 mmol). The reaction mass was stirred at RT for 2-3 h. Followed by addition of boron trifluoride solution (1.5 mL) and continued stirring for 2 h at RT. The reaction mass was quenched in 1N HCl and basified with NaOH solution. The obtained crude product was further purified by column chromatography on silica gel eluting with 1% EtOAC:DCM eluent to afford 0.250 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 0.82-0.84 (s, 2H), 0.91-0.93 (br s, 2H), 2.24 (br s, 2H), 7.41 (t, J=6.6 Hz, 1H), 7.58-7.67 (m, 3H).

Workup

  1. stirringcontinued stirring for 2 h at RT
  2. customThe reaction mass was quenched in 1N HCl
  3. customThe obtained crude product
  4. customwas further purified by column chromatography on silica gel eluting with 1% EtOAC

Sources & evidence

ORD record
ord-ba90422df1e14b1abc8fca97ebc7fe01
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Reaction notes

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