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Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at 0℃; for 1 h; Stage #2: With sodium hydroxide In water at 0℃; for 0.5 h;
A mixture of 0. 54 g of g-4 and 10ml tetrahydrofurane (THF) was stirred at 0°C under a nitrogen atmosphere. The mixture of 0. 16g of lithium aluminium hydride and 5ml of ether was added drop wise. After lhour at 0°C water and 20percent sodium hydroxide were added, and stirred during 30 minutes. The mixture was filtered over decalite and the solvent was removed by azeotropique distillation with toluene yielding 0.3g (69percent) of thiazol-5-yl-methanol (g-5).
Reference：
[1] Patent: WO2003/97616, 2003, A1, . Location in patent: Page/Page column 26
[2] Patent: US5968942, 1999, A,
[3] Patent: US6046190, 2000, A,
With isopentyl nitrite; In tetrahydrofuran; at 120℃; for 0.333333h;
General procedure: A solution of the selected heterocyclic starting material (1.00 mmol) in THF (10 mL) and a solutionof isopentyl nitrite (141 mg, 1.20 mmol) in THF (10 mL) were both pumped at a flow rate of 0.25 mLmin1 with a Vapourtech ?Easy MedChem V3? system, meeting at a PTFE T-piece and the outputflowing through a 10.0 mL coil reactor maintained at 120 C, giving a residence time of 20 min.The pressure of the system was maintained at 7 bar with a back-pressure regulator. For compoundswhere an isolated yield was reported: the output mixture was concentrated under reduced pressureto give an oil (or powder). The oil (or powder) was purified using column chromatography withvarious mixtures of ethyl acetate and hexane as the eluent, or by recrystallisation using methanol, togive isolated compounds that showed no impurities by NMR spectroscopy. For compounds where aconversion was reported (due to volatility of products), the output mixture was carefully concentratedunder a reduced pressure of 100 mbar for 10 min and the conversion was calculated by integration ofproduct peaks to a quantified internal standard (nitrobenzene).
48%
With isopentyl nitrite; In 1,4-dioxane; at 80℃; for 2h;Heating / reflux;
The mixture of 2. 15g of isoamyl nitrite and 10ml of dioxane was stirred at 80C under a nitrogen atmosphere. A solution of 1.23g of g-3 in 20ml of dioxane was added drop wise. The mixture was refluxed for 2 hours. After cooling to room temperature 30ml of ethyl acetate was added. The mixture was washed with brine and dried and the solvent evaporated under reduced pressure. The crude product is purified on silica, yielding 0.54g (48%) of thiazol 5-carboxylic acid methyl ester (g-4).
Part B Preparation of Methyl 5-thiazolecarboxylate To a solution of 35 mL (30.5 g, 260 mmol) of isoamyl nitrite in 120 mL of dioxane at 80 C. under nitrogen, was slowly added a slurry of 20.0 g (126 mmol) of <strong>[6633-61-0]methyl 2-amino-5-thiazolecarboxylate</strong> over a 45 minute period. After refluxing for a further 1 hour, the solution was cooled, concentrated, dissolved in ethyl acetate, washed with saturated sodium bicarbonate, brine, dried over magnesium sulfate, filtered and concentrated to afford 28 g of the crude product. This was chromatographed on 400 g of silica gel using 20% ethyl acetate/hexane to afford 9.07 g of purified material, which was crystallized from methylene chloride/hexane to yield 7.64 g of pure methyl 5-thiazolylcarboxylate, m/e=144(M+H).
(A) Preparation of methyl thiazole-5-carboxylate Methyl 2-aminothiazole-5-carboxylate (79 g, 0.5 mol) was added over a period of 2 hours to a boiling solution of amyl nitrite (117.0 g, 1.0 mol) in dioxan (1 liter). After refluxing for a further half hour, the solvent was removed under reduced pressure and the residue was steam distilled to give a yellow oil which, on trituration with petroleum ether, gave the desired product as a white solid (32.0 g), m.pt. 68 C.
With tert.-butylhydroperoxide; ferrous(II) sulfate heptahydrate; sulfuric acid; In water; at 25.0℃;
A solution of FeSO4·7H2O (33.4 g, 120 mmol) in 80 ml H2O and 70% tert-butyl hydroperoxide (12 ml, 120 mmol) were added to a stirred and cooled (10-20 ) mixture of the methyl-thiazole-5-carboxylate 6 (2.86 g, 20 mmol), 4 M H2SO4 (10 ml), and the 40% aldehyde (13.22 g, 120 mmol) separately and simultaneously. The reaction mixture was stirred at room temperature (25 ) for 1 h, extracted with EtOAc and washed with saturated Na2S2O3 solution and brine. After drying over anhydrous Na2SO4 and removing the solvent, a crude material was obtained. The material was purified by column chromatography (PE:EtOAc, 50:1, v/v) to afford compound 7 (2.97 g, 80%) as pale yellow solid. MS (ESI) m/z 186.0 [M+H]+. 1H NMR (400 Hz, CDCl3) δ 8.50 (s, 1H), 3.95 (s, 3H), 2.73 (s, 3H) .
80%
With tert.-butylhydroperoxide; ferrous(II) sulfate heptahydrate; sulfuric acid; In water; at 20.0℃; for 2.25h;Inert atmosphere;
At 0 C ice bath,5-thiazole methyl ester 1a(2.86g, 20mmol)Dissolved in 10ml of 4M sulfuric acid solution (2.0 eq),FeSO4 7H2O (33.4 g, 6.0 eq) was added in that order.40% aqueous acetaldehyde solution (13.22 g, 6.0 eq), protected under N2 70% t-BuOOH (12 ml, 6.0 eq) was slowly added dropwise via a constant pressure funnel.After 15 minutes, the drop is completed.Transfer to room temperature for 2 h, extract with EA (60 ml x 3),Wash the saturated FeSO4 solution twice,Water, saturated NaHCO3 solution,Wash the saturated saline once,Dry anhydrous Na2SO4,Evaporate the solvent under reduced pressure.Column chromatography separation (PE: EA = 50: 1 v/v) gave a pale yellow odorous solid 1b(2.97g, 80%).
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