Dicyclohexylcarbodiimide → alphahydroxy-N-[1-methyl-4-(3-pyridinyl)butyl]benzeneacetamide

Temperature

-5 °C

To a cooled (-5° C.) solution of 32 g of the above enriched amine, 33 g of 1-hydroxybenzotriazole and 31.22 g of (R)-mandelic acid in 350 mL of dimethylformamide, was added a solution of 44.26 g of 1,3-dicyclohexylcarbodiimide in 150 mL of dimethylformamide and the mixture was stirred at -5° C. for 18 hours. After the precipitated dicyclohexylurea was removed by filtration, the filtrate was evaporated and the residue dispersed in 300 mL of cold 2N sodium hydroxide. The resulting solids were removed by filtration, washed with dilute sodium hydroxide solution and with water and then dissolved in 500 mL of 2N hydrochloric acid. The acidic solution was extracted with dichloromethane (3×150 mL) to remove neutral impurities, then was basified with 10N sodium hydroxide and extracted with dichloromethane (6×300 mL). The dried extracts were evaporated to give 55 g of residual solid. Crystallization of the product from ethanol gave 25.6 g of [ R-(R*,R)]-alpha-hydroxy-N-[1-methoxy-4-(3-pyridinyl)butyl]benzeneacetamide, mp 141°-143° C. An additional 1.3 g of product, mp 141°-143° C., was obtained from the mother liquors.

1. customAfter the precipitated dicyclohexylurea was removed by filtration
2. customthe filtrate was evaporated
3. additionthe residue dispersed in 300 mL of cold 2N sodium hydroxide
4. customThe resulting solids were removed by filtration
5. washwashed with dilute sodium hydroxide solution and with water
6. dissolutiondissolved in 500 mL of 2N hydrochloric acid
7. extractionThe acidic solution was extracted with dichloromethane (3×150 mL)
8. customto remove neutral impurities
9. extractionextracted with dichloromethane (6×300 mL)
10. customThe dried extracts were evaporated

ORD record

ord-2072e0ac6c8549e8b89f1348c2b8c0aa

Source dataset

uspto-grants-1988_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04786646