Triethylamine → (trans)-3-Methyl-4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1012010ノート

反応式

HRID 1012010 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl[CH2:24][CH2:25][CH2:26][C:27](Cl)=[O:28].[H-].[Na+]>C(Cl)Cl.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([N:14]2[CH2:24][CH2:25][CH2:26][C:27]2=[O:28])[C@H:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3].[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([N:14]2[CH2:24][CH2:25][CH2:26][C:27]2=[O:28])[C@H:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 783704-Chlorobutyryl chlorideHCID 51358548tert-Butyl 4-amino-3-methylpiperidine-1-carboxylate

生成物 2

HCID 67313620(trans)-3-Methyl-4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester収率 39%HCID 67314227(cis)-3-Methyl-4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester収率 18%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To an ice-cold solution of 4-amino-3-methyl-piperidine-1-carboxylic acid tert-butyl ester (2.5 g 12 mmol) and triethylamine (31 ml, 23 mmol) in CH2Cl2 (100 ml) was added 4-chlorobutyric acid chloride (11 ml, 14 mmol) and the reaction allowed to come to room temperature. The reaction was then washed with water, was dried (Na2SO4) and concentrated. The crude amide (1.9 g, 6 mmol) was redissolved in DMF (50 ml), cooled to 0° C. and sodium hydride (0.3 g, 12 mmol) was added portionwise. The mixture was allowed to reach room temperature, the reaction concentrated and the residue redissolved in CH2Cl2 and washed with saturated sodium hydrogen carbonate, dried (Na2SO4) and concentrated. Flash column chromatography (EtOAc:n-heptane 9:1-95:5) separated the title compounds affording (cis)-3-Methyl-4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (0.3 g, 18%) and (trans)-3-methyl-4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (0.63 g, 39%) as yellow oils. MS: 283.4 (MH+).

後処理

  1. customto come to room temperature
  2. washThe reaction was then washed with water
  3. dry with materialwas dried (Na2SO4)
  4. concentrationconcentrated
  5. customto reach room temperature
  6. concentrationthe reaction concentrated
  7. dissolutionthe residue redissolved in CH2Cl2
  8. washwashed with saturated sodium hydrogen carbonate
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customFlash column chromatography (EtOAc:n-heptane 9:1-95:5) separated the title compounds

出典と根拠

ORDレコード
ord-6fb324ea0b4d4a25abd95aa453861ff7
出典データセット
uspto-grants-2011_07
特許番号
US07977358B2

反応ノート

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