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 4 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 1N HCl (2×50 mL) and brine (2x50 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 4 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 1N HCl (2×50 mL) and brine (2x50 mL)
10. dry with materialThe organic layer is dried over magnesium sulfate
11. customevaporated

ORD record

ord-5385f06c6d4a40068a8028ebeb3cb2e2

Source dataset

uspto-grants-1991_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04990533