4-Chlorothiazole-5-carboxaldehyde

Synthesis of 4-chlorothiazole-5-carbaldehyde (333): To a stirred solution of compound 332 (1.1 g, 5.75 mmol) in THF (10 mL) was added 5 N aqueous HC1 in 1, 4-dioxane (6 mL) at 0 °C; warmed to RT and stirred for 3 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was poured into brine (20 mL) extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with saturated sodium bicarbonate (100 mL) dried over sodium sulfate, filtered and concentrated in vacuo to afford compound 333 (800 mg, 95percent) as yellow oil. TLC: 10percent EtOAc/ hexanes (R 0.3); 1H NMR (CDC13, 500 MHz): ö 10.11 (s, 1H), 9.00 (s, 1H).Step 4. 4-chloro-1, 3-thiazole-5-carbaldehydeTo a solution of 4-chloro-5-(1, 3-dioxolan-2-yl)-1, 3-thiazole (0.75 g, 3.9 mmol) in THF (10 mL) was added 5.0 M of HCl solution in water (2 mL, 10 mmol). The resulting mixture was stirred at ambient temperature for 2 h. The reaction solution was poured into brine and extracted with ethyl acetate three times. The combined extracts were washed with saturated sodium bicarbonate, brine, dried over MgSOAdd 5 N HC1 (50 mL, 250 mmol) to a stirred solution of 4-chloro-5- [1, 3] dioxolan-2- yl-thiazole (19.2482 g, 100 mmol) and tetrahydrofuran (250 mL). Stir the reaction for 1.5 h at room temperature. Pour the reaction into brine (300 mL) and extract with ethyl acetate (3 X 100 mL). Wash the ethyl acetate with saturated sodium bicarbonate (150 mL) and then with brine (100 mL). Dry the ethyl acetate over sodium sulfate and filter off the sodium sulfate. Concentrate on a rotary evaporator and purify the crude product by flash chromatography on silica gel eluting with 20 percent ethyl acetate/hexanes to yield 13. 09 g (88percent) of4-chloro-thiazole-5-carbaldehyde : IHNMR (CDCl3) : 5 = 10. 13 (s, 1H), 9.04 (s, 1H).c) Step 5. [000274] Synthesis of (4-chlorothiazol-5-yl) methanol (334): To a stirred solution of compound 333 (750 mg, 5.10 mmol) in dry THF (20 mL) under inert atmosphere was added lithium aluminium hydride (193 mg, 5.10 mmol) at 0 °C; warmed to RT and stirred for 3 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was cooled to 0 °C, quenched with 30percent aqueous sodium hydroxide solution (3 mL) extracted with EtOAc (2 x 100 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to afford compound 334 (520 mg, 68percent) as yellow oil. TLC: 10percent EtOAc/ hexanes (R 0.3); 1H NMR (CDC13, 500 MHz): oe 8.69 (m, 1H), 4.88 (s, 2H).To a 0°C solution of 4-chloro-l, 3-thiazole-5-carbaldehyde (1.4 g, 9.5 mmol) in anhydrous methanol (100 mL) was added sodium borohydride (570 mg, 15.2 mmol). The reaction mixture was stirred at room temperature for 3 hours. Water (20 mL) was added. MeOH was evaporated. The resultant residue was extracted with EtOAc (1 x 20 mL) and 2-butanol (1 x 20 mL). The organic extracts were combined, dried over MgSO4, filtered, evaporated, and dried in vacuo, affording (4-chloro-l, 3-thiazol-5- yl)methanol (1.3 g, 91percent yield). The product was used without further purification.

Molecular Weight:147.58
XLogP3:1.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:146.9545626
Monoisotopic Mass:146.9545626
Topological Polar Surface Area:58.2
Heavy Atom Count:8
Complexity:100
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes