Sodium hydride → Methyl 2-(1-methylpiperidin-4-yl)acetate

HRID 742324ノート

反応式

HRID 742324 の反応式
C(OP([CH2:9][C:10]([O:12][CH3:13])=[O:11])(OCC)=O)C.[H-].[Na+].[CH3:16][N:17]1[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1>C1COCC1>[CH3:16][N:17]1[CH2:22][CH2:21][CH:20]([CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH2:19][CH2:18]1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 66113Methyl diethylphosphonoacetateHCID 740491-Methyl-4-piperidone

生成物 1

HCID 19425952Methyl 2-(1-methylpiperidin-4-yl)acetate収率 28%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
60 °C

実験手順

Methyl diethylphosphonoacetate (88.69 g, 0.422 mol) was added dropwise to a stirred suspension of sodium hydride (18.56 g, 60% dispersion in oil, 0.464 mol) in THF (300 ml) under nitrogen, at such a rate as to maintain the temperature below 30° C. The mixture was stirred for 1 h and a solution of N-methyl-4-piperidinone (47.71 g, 0.422 mol) in THF (150 ml) was added dropwise. The mixture was heated at 60° C. for 4.5 h before removing the solvent under vacuum and redissolving the residue in dichloromethane (300 ml) and water (200 ml). The dichloromethane phase was separated, washed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml) and dried (MgSO4). The crude product was chromategraphed on silica gel, eluting with methanol/ether (5:95) to give the title-product (19.75 g, 28%). 1H NMR (250 MHz, CDCl3) δ (3H, s, N-CH3), 2.35 (2H, t, J=6 Hz, CH2), 2.40-2.50 (4H, m, 2 of CH2), 3.00 (2H, t, J=6 Hz, CH2), 3.70 (3H, s, CO2CH3), 5.65 (1H, s, vinyl CH).

後処理

  1. temperatureat such a rate as to maintain the temperature below 30° C
  2. custombefore removing the solvent under vacuum
  3. dissolutionredissolving the residue in dichloromethane (300 ml)
  4. customThe dichloromethane phase was separated
  5. washwashed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml)
  6. dry with materialdried (MgSO4)
  7. washeluting with methanol/ether (5:95)

出典と根拠

ORDレコード
ord-960e12df9aed4e6baf8949d4b864ad17
出典データセット
uspto-grants-1996_09
特許番号
US05554629

反応ノート

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