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

HRID 228493노트

반응식

HRID 228493 반응식
[CH2:1]([O:3][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>[NH3:8].[CH3:1][OH:3].[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]

참가 물질

7

반응물 4

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

생성물 2

HCID 21705897Ammonia methanol수율 3%HCID 597300371-(4-Methoxy-benzyl)-piperidine-3-carboxylic acid methoxy-methyl-amide수율 186.4%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매2회

실험 절차

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 NH3 MeOH 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).

후처리

  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

출처 및 근거

ORD 기록
ord-7c6236249c2f4418845e1a9fa3d49f7f
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07560463B2

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