With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.144163-97-3,4-Nitrophenyl (thiazol-5-ylmethyl) carbonate,as a common compound, the synthetic route is as follows.
Example 21 Alternative Preparation of (2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane Alternative A The product of Example 17F (9.5 g, 33.4 mmol) and phenylboronic acid (4.1 g, 33.6 mmol) were combined in toluene (150 mL) and refluxed for 2.5 hours with azeotropic water removal (Dean-Stark trap). Toluene (100 mL) was distilled out at atmospheric pressure, then the remaining toluene was removed under vacuum, to provide a yellow syrup which was dissolved in DMF (50 mL) and cooled to -60 C. A solution of 5-(p-nitrophenyloxycarbonyloxymethyl)thiazole (9.5 g, 33.5 mmol) in DMF (50 mL) was added over 45 minutes. The resulting mixture was stirred for 8 hours at -55+-5 C., then 14 hours at -25 C., then was allowed to warm to room temperature. The reaction mixture was diluted with 1 N HCl (250 mL) and washed with CH2 Cl2 (2*80 mL). The combined organic layers were back-extracted with 1 N HCl (60 mL). The combined aqueous HCl layers were cooled in an ice-bath to 2 C., and conc. (37%) HCL (30 mL) was added over 5 minutes. The desired product (bis HCl salt) began to precipitate within 30 minutes. The slurry was stirred 3 hours at 2-5 C., then the product (bis HCl salt) was collected by filtration and dried in a vacuum oven at 55-60 C. Yield 11.4 g (68%).
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Reference£º
Patent; Abbott Laboratories; US5559158; (1996); A;,
Thiazole | C3H3NS – PubChem
Thiazole | chemical compound | Britannica