Reaction #480206

Reaction equation

1-[[4-(methoxycarbonyl)-3-methylbenzoyl]oxy]-2,5-pyrrolidinedione

3-hydroxybenzylamine

triethylamine

→

4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]-2-methylbenzoic acid, methyl ester

Yield 91.3%

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   OtherThe solvent was evaporated (<0.5 mm Hg, 40° C.) and ethyl acetate (200 mL)
2. 2
   workup.ADDITIONwas added
3. 3
   WashThe solution was washed with 0.5N hydrochloric acid (200 mL), brine (200 mL), saturated sodium bicarbonate solution (2×150 mL) and brine (200 mL)
4. 4
   ExtractionEach aqueous layer was back-extracted in turn with ethyl acetate (100 mL)
5. 5
   DryingThe combined organic layers were dried (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Otherevaporated

Procedure

A solution of 1-[[4-(methoxycarbonyl)-3-methylbenzoyl]oxy]-2,5-pyrrolidinedione (Example 6; 6.00 g, 20.6 mmol), 3-hydroxybenzylamine (2.92 g, 23.7 mmol) and triethylamine (2.61 g, 25.8 mmol) in N,N-dimethylformamide (100 mL) was stirred at room temperature overnight. The solvent was evaporated (<0.5 mm Hg, 40° C.) and ethyl acetate (200 mL) was added. The solution was washed with 0.5N hydrochloric acid (200 mL), brine (200 mL), saturated sodium bicarbonate solution (2×150 mL) and brine (200 mL). Each aqueous layer was back-extracted in turn with ethyl acetate (100 mL). The combined organic layers were dried (MgSO4), filtered, and evaporated to give 4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]-2-methylbenzoic acid, methyl ester (5.63 g, 91%) as an orange liquid that solidified on standing, mp 100-103° C.

Source