Sodium hydride → Tert-butyl 4-((6-chloropyridin-3-yl)methyl)-3-oxopiperazine-1-carboxylate

HRID 79213

反応式

HRID 79213 の反応式
[H-].[Na+].[O:3]=[C:4]1[NH:9][CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24]Cl)=[CH:20][N:19]=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:17][C:18]1[N:19]=[CH:20][C:21]([CH2:24][N:9]2[CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5][C:4]2=[O:3])=[CH:22][CH:23]=1

参加物

6

反応物 4

HCID 24758Sodium hydrideHCID 1554792-Chloro-5-(chloromethyl)pyridineHCID 516892Sodium BicarbonateHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

生成物 1

HCID 58299942Tert-butyl 4-((6-chloropyridin-3-yl)methyl)-3-oxopiperazine-1-carboxylate収率 93.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a stirred ice-cooled suspension of sodium hydride, (60% dispersion in mineral oil, 0.83 g, 21 mmol) in DMF (15 mL) was added a suspension of tert-butyl 3-oxopiperazine-1-carboxylate (2.5 g, 12 mmol) in DMF (45 mL) through a syringe. The ice-H2O bath was removed and the resulting mixture, which was a suspension, was stirred at ambient temperature for 30 min. Complete dissolution was observed. 2-chloro-5-(chloromethyl)pyridine (2.0 g, 12 mmol) was added in one portion as a solid. The resulting mixture was stirred at ambient temperature for 18 h then poured into ice and saturated NaHCO3 aqueous solution. It was extracted with ethyl acetate (2×). The combined organics were washed with saturated NaHCO3 aqueous solution (3×), dried over Na2SO4, and concentrated in vacuo. The residue was subjected to combi-flash column chromatography (methanol/DCM) to give compound 358 (3.65 g, 91% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.31 (1 H, d, J=2.2 Hz), 7.65 (1 H, dd, J=8.3, 2.4 Hz), 7.33 (1 H, d, J=8.1 Hz), 4.59 (2 H, s), 4.15 (2 H, s), 3.62 (2 H, t, J=5.4 Hz), 3.29 (2 H, t, J=5.1 Hz), 1.46 (9 H, s). LCMS-ESI (POS), M/Z, M+1: Found 326.0.

後処理

  1. additionwas added
  2. customThe ice-H2O bath was removed
  3. dissolutionComplete dissolution
  4. stirringThe resulting mixture was stirred at ambient temperature for 18 h
  5. extractionIt was extracted with ethyl acetate (2×)
  6. washThe combined organics were washed with saturated NaHCO3 aqueous solution (3×)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-391f48ab7ef644f9a406328c9263738d
出典データセット
uspto-grants-2014_09
特許番号
US08841312B2

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