1,1'-Thiocarbonyldiimidazole → 3-[Boc(methyl)amino]pyrrolidine-1-carbothioamide

To a stirring solution of thiocarbonyldiimidazole (1.23 g, 6.91 mmol) in THF (10 mL) under N2 was added methylpyrrolidin-3-yl-carbamic acid tert-butyl ester (1.20 g, 5.99 mmol) in THF (7 mL). The reaction mixture was stirred at room temperature of 1 h, and then at 55° C. for 2 h. The reaction was cooled to room temperature, and most (˜14 mL) of THF was removed. The reaction was transferred to a sealable reaction tube, 2N ammonia in methanol (6 mL) was added, and the reaction was stirred at room temperature overnight. Another portion of 2N ammonia in methanol (6 mL) was added, and the reaction was heated to 45° C. for 8 h. The reaction was concentrated to ˜5 mL, and diethyl ether was added to precipitate product. The product was filtered, washed with diethyl ether, and dried to obtain 0.920 g (64.9%) of pure methyl-(1-thiocarbamoyl-pyrrolidin-3-yl)-carbamic acid tert-butyl ester (132) as a white solid.

1. waitat 55° C. for 2 h
2. temperatureThe reaction was cooled to room temperature
3. custommost (˜14 mL) of THF was removed
4. customThe reaction was transferred to a sealable reaction tube
5. addition2N ammonia in methanol (6 mL) was added
6. stirringthe reaction was stirred at room temperature overnight
7. additionAnother portion of 2N ammonia in methanol (6 mL) was added
8. temperaturethe reaction was heated to 45° C. for 8 h
9. concentrationThe reaction was concentrated to ˜5 mL, and diethyl ether
10. additionwas added
11. customto precipitate product
12. filtrationThe product was filtered
13. washwashed with diethyl ether
14. customdried

ORD-Eintrag

ord-dae82249966241809d8593ccb1f72f3c

Quelldatensatz

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06699866B2