Chlorotrimethylsilane → HCID 86730346, compound

Temperature

65 °C

1,2-Dibromoethane (0.286 mL, 3.32 mmol) was added to a suspension of zinc powder (2.12 g, 32.4 mmol) in tetrahydrofuran (10 mL) under nitrogen atmosphere at room temperature. The liquid mixture was stirred at 65° C. for 10 minutes. The reaction liquid was allowed to stand to cool to room temperature, then chlorotrimethylsilane (0.400 mL, 3.13 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. A solution of tert-butyl 3-iodoazetidine-1-carboxylate described in Production Example 26-3 (5.91 g, 20.9 mmol) in tetrahydrofuran (10 mL) was added to the reaction liquid over 5 minutes, and the mixture was stirred at room temperature for 40 minutes (a solution A). A solution of iris(dibenzylideneacetone)dipalladium(0) (382 mg, 0.418 mmol) and tri-2-furylphosphine (402 mg, 1.73 mmol) in tetrahydrofuran (10 mL) was stirred under nitrogen atmosphere at room temperature for 15 minutes, and then the previously prepared solution A was added at room temperature. Subsequently, a solution of ethyl 4-iodobenzoate (6.92 g, 25.1 mmol) in tetrahydrofuran (18.5 mL) was added under nitrogen atmosphere at room temperature. The reaction liquid was stirred at 65° C. overnight. The reaction liquid was allowed to stand to cool to room temperature, then was filtered with celite, and the resultant was washed with ethyl acetate. The filtrate was washed serially with a saturated aqueous sodium bicarbonate solution and a saturated saline solution and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration and then the filtrate was concentrated under vacuum. The residue was dissolved in dichloromethane, then the resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate=9:1-4:1) to obtain the title compound (4.35 g, 68%).

1. customThe reaction liquid
2. temperatureto cool to room temperature
3. stirringthe mixture was stirred at room temperature for 30 minutes
4. additionwas added to the reaction liquid over 5 minutes
5. customThe reaction liquid
6. stirringwas stirred at 65° C. overnight
7. customThe reaction liquid
8. temperatureto cool to room temperature
9. filtrationwas filtered with celite
10. washthe resultant was washed with ethyl acetate
11. washThe filtrate was washed serially with a saturated aqueous sodium bicarbonate solution
12. dry with materiala saturated saline solution and then dried over anhydrous sodium sulfate
13. customThe drying agent was separated by filtration
14. concentrationthe filtrate was concentrated under vacuum
15. dissolutionThe residue was dissolved in dichloromethane
16. customthe resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate=9:1-4:1)

ORD record

ord-b3f00fd11d72404ab79bbb9f1f4c02f8

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933099B2