Tetrahydrofuran → 1-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid methoxy-methyl-amide

HRID 131041ノート

反応式

HRID 131041 の反応式
C(O[C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH2:7]1)=[O:5])C.C1COCC1.Cl.[CH3:27][NH:28][O:29][CH3:30].C([Mg]Cl)(C)C>C(OCC)(=O)C>[CH3:30][O:29][N:28]([CH3:27])[C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[CH2:7]1)=[O:5]

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 3160450Ethyl 1-(4-methoxybenzyl)piperidine-3-carboxylateHCID 178418918HCID 178418918、化合物

生成物 1

HCID 597300371-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid methoxy-methyl-amide収率 93.2%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒2 回

実験手順

Combine 1-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid ethyl ester (9.3 g, 33.5 mmol), THF (200 mL), N,O-Dimethylhydroxylamine hydrochloride (4.9 g, 50.3 mmol) at −10° C. (Acetone/ice bath) under a Nitrogen atmosphere. By dropwise addition, add Isopropylmagnesium chloride (50.3 mL, 100.6 mmol). Stir the reaction for 6 hours allowing the reaction mixture to warm to room temperature. Quench the reaction mixture with sat NH4Cl (aq) and extract product from the water using Ethyl acetate. Wash the organic layer with brine and then dry over Na2SO4. Concentrate under reduced pressure and flash chromatograph using 1:1 Hexanes:Ethyl acetate and then 1:1 Hexanes:Ethyl acetate with 3% 1N NH3MeOH to give 9.13 g (93% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 1.4-1.7 (3H, m), 1.8 (1H, d), 1.9 (1H, t), 2.1 (1H, t), 2.8-3.0 (3H, m), 3.1 (3H, s), 3.5 (2H, d), 3.6 (3H, s), 3.8 (3H, s), 6.8 (2H, d), 7.2 (2H, d); MS m/z 293 (M+1).

後処理

  1. customat −10° C.
  2. additionBy dropwise addition
  3. customthe reaction for 6 hours
  4. customQuench the reaction mixture with sat NH4Cl (aq)
  5. extractionextract product from the water
  6. washWash the organic layer with brine
  7. dry with materialdry over Na2SO4
  8. concentrationConcentrate under reduced pressure and flash chromatograph

出典と根拠

ORDレコード
ord-523afb6a94f84498b6b4754769410c4c
出典データセット
uspto-grants-2008_06
特許番号
US07381719B2

反応ノート

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