반응 #2122540

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Sodium hydride

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

SEM chloride

→

title compound

수율 85.6%

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

수율 85.6%

용매

DMF

반응 조건

후처리

1. 1
   workup.ADDITIONwas added in approx. 0.1 mL increments
2. 2
   기타before being quenched with sat'd NH4Cl soln
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   세척The organic phase was washed with sat'd NaHCO3 soln
5. 5
   건조brine, dried over (Na2SO4)
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   추출The original aqueous phase was extracted twice more
9. 9
   기타the combined residue was purified by Biotage™ flash chromatography (40M column, 50 mL/min, preequilibration with 5% B for 750 mL
10. 10
    세척followed by step gradient elution with 5% B to 5% B for 150 mL, 5% B to 75% B for 1500 mL

실험 절차

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%).

출처