反応 #2122540

反応方程式

Sodium hydride

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

SEM chloride

→

title compound

収率 85.6%

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

収率 85.6%

溶媒

DMF

反応条件

後処理

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

実験手順

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%).

出典