反应详情

温度

25 °C

A solution of [2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (90 mg) in dichloromethane (1 mL) and trifluoroacetic acid (1 mL) was stirred at 25° C. for 1 hour and then concentrated in vacuo. The residue was partitioned between ethyl acetate (5 mL) and saturated aqueous potassium carbonate (5 mL). The organic phase was dried over sodium sulfate, concentrated in vacuo and redissolved in dry tetrahydrofuran (3 mL) and triethylamine (54 μL). Chloroacetyl chloride (31 μL) in dry tetrahydrofuran (1 mL) was added dropwise at 0° C. After 30 minutes the reaction was diluted with ethyl acetate (10 mL) and washed with water/brine (1:1, 3×10 mL). The organic phase was dried over sodium sulfate, concentrated in vacuo and redissolved in tert-butanol (5 mL). Potassium tert-butoxide (79 mg) was added and the reaction stirred at 25° C. for 1.5 hour. The reaction was quenched with saturated aqueous ammonium chloride (30 mL) and extracted with ethyl acetate (2×30 mL). The combined organic phases were dried over sodium sulfate, concentrated in vacuo and co-evaporated with toluene (2×5 mL). The residue was dissolved in dry toluene (5 mL) under argon and treated with sodium bis(2-methoxyethoxy)aluminium hydride (70% in toluene, 205 μL) dropwise and stirred at 25° C. for 5 hours. The reaction was quenched at 0° C. with 10% aqueous sodium hydroxide (5 mL), and the mixture was extracted with diethyl ether (2×15 mL). The combined organic phases were dried over sodium sulfate and concentrated in vacuo to furnish 60 mg (94%) of the title compound as a colorless oil. LC-MS (m/z) 182 (MH+); tR=1.06, (UV, ELSD) 78%, 98%.

1. concentrationconcentrated in vacuo
2. customThe residue was partitioned between ethyl acetate (5 mL) and saturated aqueous potassium carbonate (5 mL)
3. dry with materialThe organic phase was dried over sodium sulfate
4. concentrationconcentrated in vacuo
5. dissolutionredissolved in dry tetrahydrofuran (3 mL)
6. additionChloroacetyl chloride (31 μL) in dry tetrahydrofuran (1 mL) was added dropwise at 0° C
7. additionAfter 30 minutes the reaction was diluted with ethyl acetate (10 mL)
8. washwashed with water/brine (1:1, 3×10 mL)
9. dry with materialThe organic phase was dried over sodium sulfate
10. concentrationconcentrated in vacuo
11. dissolutionredissolved in tert-butanol (5 mL)
12. additionPotassium tert-butoxide (79 mg) was added
13. customThe reaction was quenched with saturated aqueous ammonium chloride (30 mL)
14. extractionextracted with ethyl acetate (2×30 mL)
15. dry with materialThe combined organic phases were dried over sodium sulfate
16. concentrationconcentrated in vacuo and co-evaporated with toluene (2×5 mL)
17. dissolutionThe residue was dissolved in dry toluene (5 mL) under argon
18. additiontreated with sodium bis(2-methoxyethoxy)aluminium hydride (70% in toluene, 205 μL) dropwise
19. stirringstirred at 25° C. for 5 hours
20. customThe reaction was quenched at 0° C. with 10% aqueous sodium hydroxide (5 mL)
21. extractionthe mixture was extracted with diethyl ether (2×15 mL)
22. dry with materialThe combined organic phases were dried over sodium sulfate
23. concentrationconcentrated in vacuo