Dimethylformamide → HCID 34438, compound

Temperature

80 °C

To 81 g of 5-methoxy-2,3-dihydro-3-benzofuranacetic acid in 250 ml of dichloromethane were added 0.5 ml of DMF and 48 ml of thionyl chloride. The mixture was stirred for 10 minutes and then heated at reflux for 1 hour. Dichloromethane and thionyl chloride were evaporated, and remaining traces of thionyl chloride were removed by evaporation with n-heptane. The resulting acid chloride was dissolved in 240 ml of acetone and added dropwise to a stirred solution of 25.5 g of NaN3 in 120 ml of water at 10°-15° C. Cold toluene (1500 ml) was added, and the organic phase was separated, washed with brine, dried (MgSO4) and finally placed in a 5 l beaker and heated slowly to 80° C. When the N2 evolution had ceased 600 ml of conc. hydrochloric acid and 900 ml of water were added. The resulting mixture was stirred overnight at room temperature. The water phase was separated and made alkaline (pH 10-11) by addition of ammonium hydroxide and finally extracted with dichloromethane. The organic phase was evaporated and the remaining oil was dissolved in 1000 ml of dil. hydrochloric acid. This solution was left for 16 hours and then added to 600 ml of ammonium hydroxide at 0° C. Dichloromethane was added, the organic phase was separated, dried (Na2SO4) and evaporated yielding 61 g of product as an oil.

1. temperatureheated
2. temperatureat reflux for 1 hour
3. customDichloromethane and thionyl chloride were evaporated
4. customwere removed by evaporation with n-heptane
5. dissolutionThe resulting acid chloride was dissolved in 240 ml of acetone
6. additionadded dropwise to a stirred solution of 25.5 g of NaN3 in 120 ml of water at 10°-15° C
7. additionCold toluene (1500 ml) was added
8. customthe organic phase was separated
9. washwashed with brine
10. dry with materialdried (MgSO4)
11. additionwere added
12. stirringThe resulting mixture was stirred overnight at room temperature
13. customThe water phase was separated
14. additionby addition of ammonium hydroxide
15. extractionfinally extracted with dichloromethane
16. customThe organic phase was evaporated
17. dissolutionthe remaining oil was dissolved in 1000 ml of dil. hydrochloric acid
18. waitThis solution was left for 16 hours
19. additionadded to 600 ml of ammonium hydroxide at 0° C
20. additionDichloromethane was added
21. customthe organic phase was separated
22. dry with materialdried (Na2SO4)
23. customevaporated

ORD record

ord-875cd7d07d874e9a9559abce1980cba4

Source dataset

uspto-grants-1989_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04847254