反应详情

To a stirred solution of methyl 2-methoxy-4-(1-tert-butyloxycarbonyl-3-azetidinyloxy)benzoate from Step 4 above (200 mg, 0.647 mmol) in methanol (10 mL) was added 2N NaOH (5 mL, 10 mmol). The reaction mixture was refluxed for 30 minutes, then cooled in a ice water bath. The solution was acidified with 5% citric acid then the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate and washed with water (2×25 mL). The aqueous layer was made alkaline (pH=9) with DIEA, cooled, then di-tertbutyldicarbonate (275 mg, 1.26 mmol) was added to the stirring solution. After 4 hours, the aqueous solution was extracted with diethyl ether (50 mL), and then made acidic by addition of 1N HCl (25 mL). The aqueous layer was extracted with methylene chloride (3×25 mL) and the organic layers were collected, dried (MgSO4), filtered, and the solvent was evaporated under reduced pressure. 2-Methoxy-4-(1-tert-butyloxycarbonyl-3-azetidinyloxy)benzoic acid was obtained as a white solid which was used without further purification.

1. temperatureThe reaction mixture was refluxed for 30 minutes
2. temperaturecooled in a ice water bath
3. customthe solvent was evaporated under reduced pressure
4. dissolutionThe residue was dissolved in ethyl acetate
5. washwashed with water (2×25 mL)
6. temperaturecooled
7. extractionthe aqueous solution was extracted with diethyl ether (50 mL)
8. additionmade acidic by addition of 1N HCl (25 mL)
9. extractionThe aqueous layer was extracted with methylene chloride (3×25 mL)
10. customthe organic layers were collected
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. customthe solvent was evaporated under reduced pressure