反应详情

温度

15 °C

To a -10° C. solution of potassium tert-butoxide (150 g, 1.3 mol) in THF (1.35 L) was added a solution of ethyl chloroacetate (139 mL, 1.3 mol) and ethyl formate (103 mL, 1.27 mol) in THF (150 mL) dropwise over 75 minutes, with good mechanical stirring. A THF rinse (25 mL) was added over 5 minutes. The thick solution was stirred another 3 hours at ca. -5° to 0° C.,then the reaction was quenched by addition of a solution of NaCl (240 g) and conc. HCl (90 mL) in water (960 mL). The mixture was allowed to warm to 15° C. and the lower aqueous layer was discarded. Thiourea (97 g, 1.27 mol) was dissolved in the crude THF solution of chloroaldehyde. The solution was warmed to 65° C. and refluxed for 1 hour, then cooled to 30° C. Addition of a solution of K2CO3 (88 g, 0.64 mol) in 1500 mL water produced two layers (aqueous pH=7). The THF was removed under vacuum at ≤45° C., causing the product to precipitate as a yellow solid. The slurry was cooled to 15° C., and the product was collected on a fritted Buchner funnel and washed with 3×200 mL water, then dried 24 hours in a vacuum oven at 55° C. to provide 151 g of title compound as a yellow solid, m.p. 155°-158° C. 1H NMR (DMSO-d6) δ7.8 (br s, 2H, NH2), 7.62 (s, 1H), 4.13 (q, 2H), 1.18 (t, 3H). 13C NMR (DMSO-d6) δ173.4, 161.3, 147.9, 114.5, 60.1, 14.3.

1. washA THF rinse (25 mL)
2. additionwas added over 5 minutes
3. customthe reaction was quenched by addition of a solution of NaCl (240 g) and conc. HCl (90 mL) in water (960 mL)
4. temperatureThe solution was warmed to 65° C.
5. temperaturerefluxed for 1 hour
6. temperaturecooled to 30° C
7. customproduced two layers (aqueous pH=7)
8. customThe THF was removed under vacuum at ≤45° C.
9. customto precipitate as a yellow solid
10. temperatureThe slurry was cooled to 15° C.
11. customthe product was collected on a fritted Buchner funnel
12. washwashed with 3×200 mL water
13. customdried 24 hours in a vacuum oven at 55° C.