反应详情

温度

-1 °C

To a -10° C. solution of potassium tert-butoxide (110 g, 0.98 mol) in THF (1.9 L) was added a solution of ethyl chloroacetate (100 mL, 0.934 mol) and ethyl formate (75 mL, 0.928 mol) in THF (400 mL) dropwise over 2 hours, with good mechanical stirring. The thick solution was stirred another 2 hours at ca. -1° C. then the reaction was quenched by addition of a solution of NaCl (150 g) in 1N HCL (750 mL). The mixture was allowed to warm to 20° C. and the lower aqueous layer (containing some precipitated salt) was separated. The organic layer was stripped under vacuum on a rotary evaporator. The oil was redissolved in 500 mL ethyl acetate, dried with 75 g Na2SO4 for 1 hour, filtered and concentrated under vacuum (40°-50° C. bath temperature) to an oil. The resulting crude chloroaldehyde (161 g) and thiourea (70 g, 0.92 mol) were dissolved in THF (2 L) and warmed to gentle reflux (60° C.). The thiourea dissolved during warming, and within 20 minutes, product precipitated from solution. After 100 minutes the suspension was allowed to cool to room temperature, then was cooled in an ice-bath for 1 hour. The product was collected on a fritted Buchner funnel and washed with 2×100 mL cold THF, then dried overnight in a vacuum oven at 50° C. Yield: 122 g of title compound as a tan-colored solid, m.p. 182°-185° C. (dec.). 1H NMR (DMSO-d6) δ7.86 (s, 1H), 4.19 (q, 2H), 1.21 (t, 3H). 13C NMR (DMSO-d6) δ171.9, 160.4, 140.4, 114.4, 61.1, 14.2.

1. customthe reaction was quenched by addition of a solution of NaCl (150 g) in 1N HCL (750 mL)
2. temperatureto warm to 20° C.
3. additionthe lower aqueous layer (containing some precipitated salt)
4. customwas separated
5. customThe organic layer was stripped under vacuum on a rotary evaporator
6. dissolutionThe oil was redissolved in 500 mL ethyl acetate
7. dry with materialdried with 75 g Na2SO4 for 1 hour
8. filtrationfiltered
9. concentrationconcentrated under vacuum (40°-50° C. bath temperature) to an oil
10. temperaturewarmed
11. temperatureto gentle reflux (60° C.)
12. temperatureduring warming
13. waitwithin 20 minutes
14. customproduct precipitated from solution
15. waitAfter 100 minutes the suspension was allowed
16. temperatureto cool to room temperature
17. temperaturewas cooled in an ice-bath for 1 hour
18. customThe product was collected on a fritted Buchner funnel
19. washwashed with 2×100 mL cold THF
20. customdried overnight in a vacuum oven at 50° C