Imidazole → (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)-3-cyclopropylbut-3-en-2-ylcarbamate

Temperature

80 °C

To a solution of (S)-tert-butyl 4-(1-cyclopropylvinyl)-2,2-dimethyloxazolidine-3-carboxylate (Intermediate 232, 8.25 g, 30.86 mmol) in methanol (100 mL) at room temperature was added p-toluenesulfonic acid monohydrate (1.174 g, 6.17 mmol). The reaction mixture was heated to 80° C. overnight. Another 0.2 eq of p-toluenesulfonic acid monohydrate was added. Continue heating at 80° C. for 2 hours. The reaction mixture was cooled to room temperature. Triethylamine (4.29 mL, 30.86 mmol) and di-tert-butyl dicarbonate (3.37 g, 15.43 mmol) were added. The reaction mixture was stirred over the weekend then concentrated. The residue was dissolved in ethyl acetate and washed once with saturated sodium bicarbonate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated. The resulting oil was dissolved in DCM (100 mL). Imidazole (2.73 g, 40.11 mmol), 4-dimethylaminopyridine (0.754 g, 6.17 mmol) and tert-butyldimethylsilyl chloride (4.65 g, 30.86 mmol) were added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was filtered to remove solids and washed with brine twice. The organic layer was dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (0%-10% ethyl acetate/hexanes) afforded the title compound as a colorless oil (6.77 g, 64%).

1. temperatureContinue heating at 80° C. for 2 hours
2. temperatureThe reaction mixture was cooled to room temperature
3. concentrationthen concentrated
4. dissolutionThe residue was dissolved in ethyl acetate
5. washwashed once with saturated sodium bicarbonate
6. dry with materialThe combined organic extracts were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. dissolutionThe resulting oil was dissolved in DCM (100 mL)
10. stirringthe reaction mixture was stirred overnight at room temperature
11. filtrationThe reaction mixture was filtered
12. customto remove solids
13. washwashed with brine twice
14. dry with materialThe organic layer was dried over magnesium sulfate
15. filtrationfiltered
16. concentrationconcentrated

ORD record

ord-9ecad479b36e4d43a33545a9af50a967

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309245B2