1-bromo-3-methylbutan-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of compound 35 (3.5 g, 1.25 eq.) and ethylthioxamate (2.3 g, 1 eq.) in ethanol (40 mL) was heated to 80° C. for 6 hrs, and then cooled to 0° C. The reaction mixture was diluted with water and EtOAc, and then neutralized to pH 7 with NH3 (28%). The aqueous layer was extracted with EtOAc. The combined organic layers were dried over sodium sulfate and then removed under reduced pressure. The residue was purified by chromatography on silica gel to yield compound 36 as yellow oil in quantitative yield. The aqueous layer was extracted with EtOAc The combined organic layers were dried over sodium sulfate removed under reduced pressure The residue was purified by chromatography on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of compound 211 (3.5 g, 1.25 eq.) and ethylthioxamate (2.3 g, 1 eq.) in ethanol (40 mL) was heated to 80° C. for 6 hrs, and then cooled to 0° C. The reaction mixture was diluted with water and EtOAc, and then neutralized to pH 7 with NH3 (28%). The aqueous layer was extracted with EtOAc. The combined organic layers were dried over sodium sulfate and then removed under reduced pressure. The residue was purified by chromatography on silica gel to yield compound 212 as yellow oil in quantitative yield. 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 1.25 (d, J=6.73 Hz, 6H), 1.31 (t, J=7.24 Hz, 3H), 3.11 (hep, J=6.73 Hz, 1H), 4.35 (q, J=7.24 Hz, 2H), 7.72 (s, 1H). The aqueous layer was extracted with EtOAc The combined organic layers were dried over sodium sulfate removed under reduced pressure The residue was purified by chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution composed of 2.0 g of (E)-3-(2-chloro-5-nitrophenyl)-2-propenethioamide, 3.0 g of 1-bromo-3-methyl-2-butanone and 25 ml of ethyl alcohol was warmed to gentle reflux for 5 hr. The volatiles were then removed in vacuo and the residual materials separated by chromatography over 100 g of alumnia using methylene chloride as the eluant to yield (E)-2-[2-(2-chloro-5-nitrophenyl)ethenyl]-4-(1-methylethyl)thiazole as a yellow solid; m.p. 86°-89° C. was warmed to gentle reflux for 5 hr The volatiles were then removed in vacuo the residual materials separated by chromatography over 100 g of alumnia using methylene chloride as the eluant

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the above prepared 1-bromo-3-methyl-butan-2-one (3.58 g, 21.6 mmol) in 40 mL of ethanol was added thiourea (1.64 g, 1.00 eq.) and the mixture vigorously stirred at 55-60° C. for 3 h. Pouring onto crashed ice/Na2CO3, twofold extraction with ethyl acetate, washing with water and brine, drying over sodium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane/ethyl acetate=6/4), left 2.996 g of the title product as colorless oil. Pouring ice/Na2CO3, twofold extraction with ethyl acetate washing with water and brine drying over sodium sulfate, and evaporation of the solvents left 2.996 g of the title product as colorless oil

Conditions: temp:57.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of the above prepared 1-bromo-3-methyl-butan-2-one (3.58 g, 21.6 mmol) in 40 mL of ethanol was added thiourea (1.64 g, 1.00 eq.) and the mixture vigorously stirred at 55-60° C. for 3 h. Pouring onto crashed ice/Na2CO3, twofold extraction with ethyl acetate, washing with water and brine, drying over sodium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane/ethyl acetate=6/4), left 2.996 g of the title product as colorless oil. Pouring ice/Na2CO3, twofold extraction with ethyl acetate washing with water and brine drying over sodium sulfate, and evaporation of the solvents left 2.996 g of the title product as colorless oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step B) A neat solution of 5.58 g (34 mmol) of 1-Bromo-3-methyl-butan-2-one and 4.50 g (34 mmol) of ethyl thioxamate (Aldrich) was heated at 70° C. over 18 h and then cooled to room temperature. The mixture was partitioned between sat. aqueous NaHCO3 and EtOAc, the EtOAc layer dried (MgSO4), concentrated and chromatographed over SiO2 (eluted with 2% to 40% EtOAc/hexanes) to afford 3.4 g (48% overall) of 4-isopropylthiazole-2-carboxylic acid ethyl ester as an oil: 1H NMR (500 MHz, CDCl3) δ 1.32 (d, J=7 Hz, 6H), 1.42 (t, J=7.2 Hz, 3H), 3.23 (m, 1H), 4.46 (q, J=7.2 Hz, 2H), 7.18 (s, 1H). The mixture was partitioned between sat. aqueous NaHCO3 and EtOAc the EtOAc layer dried (MgSO4) concentrated chromatographed over SiO2 (eluted with 2% to 40% EtOAc/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of compound 211 (3.5 g, 1.25 eq.) and ethylthioxamate (2.3 g, 1 eq.) in ethanol (40 mL) was heated to 80° C. for 6 hrs, and then cooled to 0° C. The reaction mixture was diluted with water and EtOAc, and then neutralized to pH 7 with NH3 (28%). The aqueous layer was extracted with EtOAc. The combined organic layers were dried over sodium sulfate and then removed under reduced pressure. The residue was purified by chromatography on silica gel to yield compound 212 as yellow oil in quantitative yield. 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 1.25 (d, J=6.73 Hz, 6H), 1.31 (t, J=7.24 Hz, 3H), 3.11 (hep, J=6.73 Hz, 1H), 4.35 (q, J=7.24 Hz, 2H), 7.72 (s, 1H). The aqueous layer was extracted with EtOAc The combined organic layers were dried over sodium sulfate removed under reduced pressure The residue was purified by chromatography on silica gel