tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-((1-methyl-1H-imidazol-5-yl)methyl)piperazine-1-carboxylate

HRID 416918

反応式

HRID 416918 の反応式
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:14][N:15]1[C:19]([CH:20]=O)=[CH:18][N:17]=[CH:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:14][N:15]1[C:19]([CH2:20][N:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]2)=[CH:18][N:17]=[CH:16]1

参加物

5

反応物 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 5735921-methyl-1H-imidazole-5-carbaldehydeHCID 5049666Sodium triacetoxyborohydride

生成物 1

HCID 57897271tert-Butyl 4-((1-methyl-1H-imidazol-5-yl)methyl)piperazine-1-carboxylate収率 22%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

N-Boc-piperazine (0.930 g, 5.0 mmol, 1.1 eq) was dissolved in 1,2-DCE (14 mL). To this solution, 1-methyl-1H-imidazole-5-carboxaldehyde (0.500 g, 4.54 mmol, 1 eq) was added followed by the portionwise addition of sodium triacetoxyborohydride (1.35 g, 6.36 mmol, 1.4 eq). The mixture was stirred at room temperature for 4 h and was then washed with a saturated aqueous solution of NaHCO3. The organic layer was dried (MgSO4), and the solvent removed in vacuo. The crude mixture was redissolved in 18 mL of DCM and gently stirred overnight in the presence of PS-isocyanate (2 g, loading: 1.58 mmol/g). The mixture was filtered off, and the resin washed with DCM (2×10 mL). The solvent was removed in vacuo and the resulting mixture was purified by column chromatography on a Biotage SP1 system eluting with methanol (2-10%) in dichloromethane to give the title compound (0.280 g, 22%); 1H-NMR (500 MHz, CDCl3): δ 1.45 (s, 9H, C(CH3)3), 2.28-2.40 (m, 4H, piperazine N(CH2)2), 3.38 (m, 4H, piperazine N(CH2)2), 3.44 (s, 2H, NCH2), 3.66 (s, 3H, imidazole Me), 6.87 (s, 1H, imidazole 4-H), 7.40 (s, 1H, imidazole 2-H); GC-MS (Cl, m/z): Rt=4.89 min—281 [(M+H)+, 100%].

後処理

  1. washwas then washed with a saturated aqueous solution of NaHCO3
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe solvent removed in vacuo
  4. dissolutionThe crude mixture was redissolved in 18 mL of DCM and gently stirred overnight in the presence of PS-isocyanate (2 g, loading: 1.58 mmol/g)
  5. filtrationThe mixture was filtered off
  6. washthe resin washed with DCM (2×10 mL)
  7. customThe solvent was removed in vacuo
  8. customthe resulting mixture was purified by column chromatography on a Biotage SP1 system
  9. washeluting with methanol (2-10%) in dichloromethane

出典と根拠

ORDレコード
ord-1599976c7b1a445c8a540ce757e12f85
出典データセット
uspto-grants-2012_01
特許番号
US08088761B2

関連ノート

読み込み中…