반응 #640620

반응 방정식

lithium hydroxide monohydrate

Lithium hydroxide monohydrate

ethyl 4-isopropyl-thiazole-2 carboxylate

→

title product

수율 71.2%

4-Isopropyl-thiazole-2-carboxylic acid

수율 71.2%

용매

water

tetrahydrofuran

methanol

반응 조건

후처리

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe reaction mixture stirred for a further 3 hours
3. 3
   세척washed with diethyl ether (40 mL)
4. 4
   온도The aqueous phase was cooled to 0° C.
5. 5
   workup.ADDITIONacidified to pH 3 by slow addition of 1M hydrochloric acid
6. 6
   추출The aqueous layer was extracted with diethyl ether (3×50 mL)
7. 7
   건조dried over sodium sulphate
8. 8
   여과filtered
9. 9
   기타the solvent removed under vacuum
10. 10
    기타to give

실험 절차

Lithium hydroxide monohydrate (0.947 g, 22.6 mmol., 1.1 eq.) was added to a solution of ethyl 4-isopropyl-thiazole-2 carboxylate (4.08 g, 20.5 mmol., 1.0 eq.) in tetrahydrofuran (45 mL) and methanol (15 mL). The reaction mixture was stirred at ambient temperature for 15 hours. LCMS analysis of the reaction mixture showed a small amount of methyl ester remaining (trans-esterification from ethyl to methyl ester occurred) so lithium hydroxide monohydrate (86 mg, 2.0 mmol., 0.1 eq.) was added and the reaction mixture stirred for a further 3 hours. The reaction mixture was diluted with water (15 mL) and washed with diethyl ether (40 mL). The aqueous phase was cooled to 0° C., and acidified to pH 3 by slow addition of 1M hydrochloric acid. The aqueous layer was extracted with diethyl ether (3×50 mL). The organic extracts were combined, dried over sodium sulphate, filtered and the solvent removed under vacuum to give a mixture of the title product 2.5 g (71%) and 0.6 g of the decarboxylated by product. The mixture was used in the next step without further purification. 1H NMR (250 MHz, CDCl3) δ ppm 7.29 (s, 1 H) 3.15-3.30 (spt, J=6.85 Hz, 1 H), 1.35 (d, J=6.85 Hz, 6 H). LC-MS: 72% (UV), tR 1.21 min, m/z [M+1]+ 171.95.

출처