反应详情

To an ice-water bath cooled solution of 4-(4-chloro-3-fluoro-phenoxy)-2-{[(2,4-dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-benzoic acid ethyl ester (2.529 g) in THF (20 mL) was added a solution of potassium tert-pentoxide (4.5 mL, 1.7 M in toluene); the mixture was stirred at rt for 60 min after addition; then the mixture was quenched with 2 M HCl, diluted with EtOAc and water, EtOAc phase was separated and washed with water, diluted NaCl solution and dried over anhydrous sodium sulphate, filtered off, concentrated to give the desired cyclized intermediate. This intermediate was then dissolved in DCM (30 mL) and treated with thionyl chloride (0.63 mL) overnight. Then concentrated, the residue was dissolved in EtOAc, washed with water, diluted NaCl solution, then dried over sodium sulphate, filtered, concentrated and the residue was column purified to give the desired product (580 mg). LC MS ESI: 362 (M+1)+.

1. additionafter addition
2. customthen the mixture was quenched with 2 M HCl
3. additiondiluted with EtOAc and water, EtOAc phase
4. customwas separated
5. washwashed with water, diluted NaCl solution
6. dry with materialdried over anhydrous sodium sulphate
7. filtrationfiltered off
8. concentrationconcentrated
9. customto give the
10. concentrationThen concentrated
11. dissolutionthe residue was dissolved in EtOAc
12. washwashed with water, diluted NaCl solution
13. dry with materialdried over sodium sulphate
14. filtrationfiltered
15. concentrationconcentrated
16. custompurified