Methyl Anthranilate → Methyl 2-[(2,2,2-trifluoroethyl)amino]benzoate

HRID 53258

Reaction equation

HRID 53258 reaction equation
[C:1]([O:10][CH3:11])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].ClC(Cl)(Cl)S(O[CH2:18][C:19]([F:22])([F:21])[F:20])(=O)=O>C1(C)C=CC=C(C)C=1>[F:20][C:19]([F:22])([F:21])[CH2:18][NH:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[C:1]([O:10][CH3:11])=[O:9]

Participants

4

Reactant 2

HCID 8635Methyl AnthranilateHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonate

Product 1

HCID 14797319Methyl 2-[(2,2,2-trifluoroethyl)amino]benzoate

Reagents, catalysts & solvents 1

HCID 7929M-XyleneSolvent

Procedure

A solution of methyl anthranilate (98.3 g) and trifluoroethyl trichloromethanesulphonate (91.5 g) in m-xylene (200 ml) was heated at reflux for 3 h under nitrogen. The reaction mixture was allowed to cool overnight, then filtered from a white solid, washing well with diethyl ether. The combined filtrates were evaporated in vacuo and the residual oil purified by flash chromatography (silica gel, 10% diethyl ether/hexane) to give methyl 2-[N-(2,2,2-trifluoroethyl)]aminobenzoate, contaminated with trifluoroethyl trichloromethanesulphonate. To a solution of this mixture (35.8 g) in dichloromethane (150 ml), cooled to 1° C. under nitrogen, was added dropwise bromoacetyl bromide (10.1 ml), keeping the temperature below +3° C. The reaction mixture was stirred at 0°±3° C. for 12 min, then 4N NaOH solution (33.4 ml) was added dropwise over 18 min. The cooling bath was removed and the reaction mixture was stirred at room temperature for 4 h. More bromoacetyl bromide (1.6 ml) was added dropwise and the mixture was stirred for a further 6 h. After leaving to stand overnight, the organic layer was separated, washed with 10% citric add (30 ml), brine (30 ml), saturated potassium carbonate solution (30 ml) and brine (30 ml), dried (Na2SO4) and evaporated in vacuo to leave a yellow oil. This was purified by flash chromatography (silica gel, 20-25% EtOAc/petroleum ether) to afford the title compound (27.4 g). 1H NMR (CDCl3) δ3.58 (1H, d, J=11.4 Hz), 3.64 (1H, d, J=11.3 Hz), 3.83 (1H, m), 3.90 (3H, s), 4.79 (1H, m), 7.49 (1H, d, J=7.8 Hz), 7.57 (1H, t of d, J=7.6 and 1.3 Hz), 7.68 (1H, t of d, J=7.6 and 1.7 Hz), 8.09 (1H, dd, J=7.8 and 1.6 Hz). MS (CI+, NH3) m/e 373/371 (M+NH4)+.

Workup

  1. temperatureat reflux for 3 h under nitrogen
  2. temperatureto cool overnight
  3. filtrationfiltered from a white solid
  4. washwashing well with diethyl ether
  5. customThe combined filtrates were evaporated in vacuo
  6. customthe residual oil purified by flash chromatography (silica gel, 10% diethyl ether/hexane)

Sources & evidence

ORD record
ord-9b929a7c77e142d3a2425663018004a9
Source dataset
uspto-grants-1997_04
Patent number
US05618812

Linked notes

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