反应详情

A mixture of 4-[(2-fluoro-4-hydroxy-phenylamino)-methyl]-2-methyl-benzoic acid methyl ester (1.89 g, 6.53 mmol) and 37% formaldehyde (2.0 mL) in acetic acid (20 mL) is stirred for 40 minutes. Sodium triacetoxyborohydride (2.80 g, 13.2 mmol) is added and stirred at room temperature. Upon completion of the reaction, the mixture is concentrated and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous layer is separated and extracted with ethyl acetate (3×). The combined ethyl acetate layers are dried (MgSO4) and concentrated under reduced pressure. The residue is purified on 120 g silica eluting with a gradient of ethyl acetate in heptane (10% to 60%) to provide the titled compound (1.0 g, 51%) as a white solid. LC-ES/MS m/e 304.0 (M+1).

1. stirringstirred at room temperature
2. customUpon completion of the reaction
3. concentrationthe mixture is concentrated
4. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
5. customThe aqueous layer is separated
6. extractionextracted with ethyl acetate (3×)
7. dry with materialThe combined ethyl acetate layers are dried (MgSO4)
8. concentrationconcentrated under reduced pressure
9. customThe residue is purified on 120 g silica eluting with a gradient of ethyl acetate in heptane (10% to 60%)