反应详情

To 500 mL three-necked round bottom flask were added 2-methyl THF (720 mL) and an aqueous solution of sodium carbonate (2 M, 367 mL, 734 mmol). The solution was degassed for 30 min. The product of Step 1 (90 g, 367 mmol), Intermediate 1 (86 g, 367 mmol) and PdCl2(dppf) (8.05 g, 11 mmol) were added to the degassed solution under N2(g). The resulting mixture was stirred for 5 min at room temperature and was then heated to 80° C. After ca. 9 hours, the heating mantle was removed and the reaction was cooled to 30° C. The reaction mixture was filtered through a pad of SolkAFloc employing water (500 mL) and ethyl acetate (500 mL) to complete the transfer. The filtrate was then transferred to a separatory funnel, using an additional 500 mL ethyl acetate and 250 mL brine to complete the transfer. The layers were cut, the organic washed with a mixture of water and brine (500 mL and 250 mL, respectively), and then the aqueous was back extracted with ethyl acetate (400 mL). The organics were combined, dried over MgSO4 (100 g), filtered, and concentrated in vacuo to yield a brown crystalline solid. This material was recrystallized from hot ethyl acetate (250 mL at 60° C.), using hexanes as a counter-solvent (750 mL) to yield 1-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]cyclobutanol (88 g, 338 mmol, 92%). MS APCI: [M+H]+ m/z 261.2. 1H NMR (500 MHz, DMSO-D6) δ 7.87 (s, 1H), 6.59 (s, 1H), 6.58 (s, 1H), 6.45 (s, 1H), 6.34 (s, 1H), 5.14 (s, 2H), 2.52-2.48 (m, 2H), 2.31 (q, J=9.3, 2H), 2.17 (s, 3H), 1.93-1.80 (m, 2H).

1. customThe solution was degassed for 30 min
2. temperaturewas then heated to 80° C
3. waitAfter ca. 9 hours
4. customthe heating mantle was removed
5. temperaturethe reaction was cooled to 30° C
6. filtrationThe reaction mixture was filtered through a pad of SolkAFloc
7. customThe filtrate was then transferred to a separatory funnel
8. washthe organic washed with a mixture of water and brine (500 mL and 250 mL
9. extractionrespectively), and then the aqueous was back extracted with ethyl acetate (400 mL)
10. dry with materialdried over MgSO4 (100 g)
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customto yield a brown crystalline solid
14. customThis material was recrystallized from hot ethyl acetate (250 mL at 60° C.)