Chlorotrimethylsilane → N-(4-carboxybenzyl)hexanamide

Temperature

-20 °C

Hexanoic acid (3.06 g) in 20 mL acetonitrile is treated with N-methylmorpholine (2.9 mL) and the mixture cooled to -20° C. with stirring. Ethyl chloroformate (2.8 mL) is then added dropwise, keeping the temperature below or at -20° C. After stirring for an additional 40 min at that temperature, the solution is transferred to a cooled (-15° C.) solution of alpha-amino-p-toluic acid (2.0 g), triethylamine (15 mL), a chlorotrimethylsilane (5.0 mL) in methylene chloride (60 mL; prepared as described in Example 7). After the addition is complete, the mixture is stirred at 5° C. for hrs, followed by overnight stirring at room temperature. After removal of the solvents by evaporation, the residue is redissolved in methylene chloride (100 mL) and extracted with 1 N HCl (2×50 mL) and brine (2×50 mL). The organic layer is dried over magnesium sulfate and evaporated, leaving N-(4-carboxybenzyl)hexanamide as an off-white solid. The N-(4-carboxybenzyl)hexanamide product is crystallized from methanol/2N HCl, m.p. 178°-179° C.

1. customat -20° C
2. stirringAfter stirring for an additional 40 min at that temperature
3. additionAfter the addition
4. stirringthe mixture is stirred at 5° C. for hrs
5. stirringstirring at room temperature
6. customAfter removal of the solvents
7. customby evaporation
8. dissolutionthe residue is redissolved in methylene chloride (100 mL)
9. extractionextracted with 1 N HCl (2×50 mL) and brine (2×50 mL)
10. dry with materialThe organic layer is dried over magnesium sulfate
11. customevaporated

ORD record

ord-e38b38b1cd224fb886bf48367b2627aa

Source dataset

uspto-grants-1991_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05002703