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

HRID 453970ノート

反応式

HRID 453970 の反応式
[H-].[Na+].[Cl:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[NH:14][C:13]([C@@H:15]3[CH2:19][CH2:18][CH2:17][N:16]3[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[N:12][CH:11]=2)=[CH:6][N:5]=1.[CH3:27][Si:28]([CH2:31][CH2:32][O:33][CH2:34]Cl)([CH3:30])[CH3:29]>CN(C=O)C>[Cl:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[N:14]([CH2:34][O:33][CH2:32][CH2:31][Si:28]([CH3:30])([CH3:29])[CH3:27])[C:13]([C@@H:15]3[CH2:19][CH2:18][CH2:17][N:16]3[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[N:12][CH:11]=2)=[CH:6][N:5]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 57462161(S)-tert-butyl 2-(5-(2-chloropyrimidin-5-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

生成物 1

HCID 59166586(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%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

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%).

後処理

  1. additionwas added in approx. 0.1 mL increments
  2. custombefore being quenched with sat'd NH4Cl soln
  3. additiondiluted with ethyl acetate
  4. washThe organic phase was washed with sat'd NaHCO3 soln
  5. dry with materialbrine, dried over (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. extractionThe original aqueous phase was extracted twice more
  9. customthe combined residue was purified by Biotage™ flash chromatography (40M column, 50 mL/min, preequilibration with 5% B for 750 mL
  10. washfollowed by step gradient elution with 5% B to 5% B for 150 mL, 5% B to 75% B for 1500 mL

出典と根拠

ORDレコード
ord-fcd29b6a10634300aa900b053300f34b
出典データセット
uspto-grants-2013_07
特許番号
US08492553B2

反応ノート

読み込み中…