Methanol → 1-[4-Methoxycarbonyl-2-(3-pentylamino)phenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-one

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Reaction Steps

A solution of 1-(2-amino-4-methoxycarbonylphenyl)-5,5-bis-hydroxymethylpyrrolidin-2-one (0.1 g, 0.34 mmol) from Example 6 in 1 mL of dichloromethane and 0.5 mL of acetic acid was treated with 3-pentanone (0.2 g, 2.3 mmol) and sodium cyanoborohydride (0.075 g, 1.2 mmol). The resulting mixture was stirred at ambient temperature for 6 h after which time additional 3-pentanone (0.2 g, 2.3 mmol), sodium cyanoborohydride (0.075 g, 1.2 mmol) and methanol (0.5 mL) were added and stirring continued for 12 h. A third portion of 3-pentanone (0.3. g, 3.4 mmol) and sodium cyanoborohydride (0.15 g, 2.3 mmol) was added and the stirring continued for an additional 16 h. The reaction mixture was quenched with 10 mL of a saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried and concentrated. The residue was purified by chromatography (silica gel; 5% ethanol in ether) to give 0.105 g (82%) of 1-[4-methoxycarbonyl-2-(3-pentylamino)phenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-one as a white solid, mp 183-185° C.

Provenance & Evidence