Réaction #166208

Équation de réaction

3-dimethoxymethyl-2,4-difluoro-benzoic acid

2-fluoro-4-methylsulfanyl-phenyl amine

LHMDS

→

title compound

Rendement 10.8%

4-Fluoro-2-(2-fluoro-4-methylsulfanyl-phenylamino)-3-formyl-benzoic acid

Rendement 10.8%

Solvants

THF

THF

Conditions de réaction

Traitement

1. 1
   Températureto maintain the temperature below −65° C
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   AutreThe reaction was quenched by the addition of aqueous ammonium chloride
4. 4
   Autrethe products partitioned between ethyl acetate and water
5. 5
   AutreThe aqueous layer was separated
6. 6
   Extractionextracted twice with ethyl acetate
7. 7
   SéchageThe combined organic extracts were dried (Na2SO4)
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo
10. 10
    AutreThe resultant residue was triturated with diethyl ether

Mode opératoire

To a cold (−78° C.) solution of 2-fluoro-4-methylsulfanyl-phenyl amine (1.55 g, 9.9 mmol) in THF (15 mL) was added LHMDS (9.9 mL, 1.0 M solution in hexanes 9.9 mmol) dropwise so as to maintain the temperature below −65° C. After stirring for 30 minutes a solution of 3-dimethoxymethyl-2,4-difluoro-benzoic acid (700 mg, 3.0 mmol) in THF (15 mL) was added dropwise, the resultant mixture stirred cold for 3 hours then allowed to warm to room temperature and stirred for 18 hours. The reaction was quenched by the addition of aqueous ammonium chloride and the products partitioned between ethyl acetate and water. The aqueous layer was separated and acidified to pH 1 (concentrated HCl) and then extracted twice with ethyl acetate. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was triturated with diethyl ether to give the title compound as a yellow solid (105 mg, 10% yield). 1H NMR (CDCl3, 400 MHz) 10.26-10.23 (2 H, m), 8.04 (1 H, dd, J=8.76, 6.31 Hz), 7.03-6.96 (2H, m), 6.91 (1 H, d, J=1.96 Hz), 6.65 (1 H, dd, J=10.02, 8.77 Hz), 2.42 (3 H, s).

Source