反应 #2122540

反应方程式

Sodium hydride

(S)-tert-butyl 2-(5-(2-chloropyrimidin-5-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

SEM chloride

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title compound

收率 85.6%

(S)-tert-Butyl 2-(5-(2-chloropyrimidin-5-yl)-1-((2-(trimethyl-silyl)ethoxy)methyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

收率 85.6%

溶剂

DMF

反应条件

后处理

1. 1
   workup.ADDITIONwas added in approx. 0.1 mL increments
2. 2
   其他before being quenched with sat'd NH4Cl soln
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   洗涤The organic phase was washed with sat'd NaHCO3 soln
5. 5
   干燥brine, dried over (Na2SO4)
6. 6
   过滤filtered
7. 7
   浓缩concentrated
8. 8
   萃取The original aqueous phase was extracted twice more
9. 9
   其他the combined residue was purified by Biotage™ flash chromatography (40M column, 50 mL/min, preequilibration with 5% B for 750 mL
10. 10
    洗涤followed by step gradient elution with 5% B to 5% B for 150 mL, 5% B to 75% B for 1500 mL

实验过程

Sodium hydride (60% dispersion in mineral oil, 0.23 g, 5.72 mmol) was added in one portion to a stirred solution of (S)-tert-butyl 2-(5-(2-chloropyrimidin-5-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (152d-1, 2.0 g, 5.72 mmol) in dry DMF (45 mL) at ambient temperature under N2. The mixture was stirred for 5 min. before SEM chloride (1.01 mL, 5.72 mmol) was added in approx. 0.1 mL increments. The mixture was stirred for 3 h before being quenched with sat'd NH4Cl soln and diluted with ethyl acetate. The organic phase was washed with sat'd NaHCO3 soln and brine, dried over (Na2SO4), filtered, and concentrated. The original aqueous phase was extracted twice more and the combined residue was purified by Biotage™ flash chromatography (40M column, 50 mL/min, preequilibration with 5% B for 750 mL, followed by step gradient elution with 5% B to 5% B for 150 mL, 5% B to 75% B for 1500 mL, then 75% B to 100% B for 750 mL where solvent B is ethyl acetate and solvent A is hexanes). Concentration of the eluant furnished the title compound as a pale yellow foam (2.35 g, 85%).

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