Isoamyl Nitrite → Ethyl thiazole-5-carboxylate

Temperatur

25 °C

A solution of 2-amino-5-(ethoxycarbonyl)thiazole (50 g, 0.29 mmol) in a mixture of DMF (83 mL) and THF (317 mL) was added dropwise over 87 minutes to a stirred 41° C. solution of isoamyl nitrite (59 mL, 0.44 mol)in DMF (130 mL). A maximum temperature of 60° C. was observed during the exothermic addition. After another 40 minutes the THF was removed under vacuum at 45° C. The concentrated DMF solution was cooled to 25° C. and diluted with toluene (420 mL) and water (440 mL). The toluene layer was extracted with 3×120 mL water, then dried with Na2SO4 (50 g) for 1 hour. After filtration the toluene layer was stripped on a rotary evaporater at 50° C. bath temperature, then on a vacuum pump at 21° C. The crude residue containing the title compound weighed 65.6 g. This material was used directly in the next step. A sample of similarly prepared material was purified by column chromatography to give a yellow oil. 1H NMR (CDCl3) δ8.95 (s, 1H), 8.51 (s, 1H), 4.39 (q, 2H), 1.40 (t, 3H). 13C NMR (CDCl3) δ161.0, 157.9, 148.6, 129.8, 61,6, 14.1.

1. additionA maximum temperature of 60° C. was observed during the exothermic addition
2. customAfter another 40 minutes the THF was removed under vacuum at 45° C
3. additiondiluted with toluene (420 mL) and water (440 mL)
4. extractionThe toluene layer was extracted with 3×120 mL water
5. dry with materialdried with Na2SO4 (50 g) for 1 hour
6. filtrationAfter filtration the toluene layer
7. customwas stripped on a rotary evaporater at 50° C.
8. customat 21° C
9. additionThe crude residue containing the title compound
10. customA sample of similarly prepared material was purified by column chromatography
11. customto give a yellow oil

ORD-Eintrag

ord-4537884ad945454ea0660d5d6e389a65

Quelldatensatz

uspto-grants-1997_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05597927