2,3-Dihydrofuran → 1-Methoxy-4-{(tetrahydro-furan-2-yloxy)-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

HRID 1473780노트

반응식

HRID 1473780 반응식
[CH3:1][O:2][C:3]([C:5]1([N:13]([OH:26])[C:14](=[O:25])[CH2:15][C:16]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=2[CH3:24])[CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]1)=[O:4].[O:27]1[CH:31]=[CH:30][CH2:29][CH2:28]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[CH3:1][O:2][C:3]([C:5]1([N:13]([O:26][CH:28]2[CH2:29][CH2:30][CH2:31][O:27]2)[C:14](=[O:25])[CH2:15][C:16]2[C:17]([CH3:24])=[CH:18][C:19]([CH3:23])=[CH:20][C:21]=2[CH3:22])[CH2:6][CH2:7][N:8]([O:11][CH3:12])[CH2:9][CH2:10]1)=[O:4]

참가 물질

5

반응물 3

HCID 709342,3-DihydrofuranHCID 521998p-Toluenesulfonic acid monohydrateHCID 584280024-{Hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

생성물 1

HCID 584280531-Methoxy-4-{(tetrahydro-furan-2-yloxy)-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 4-{hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (compound P3ii.3 obtained in analogy to preparation example 11, step 4) (70 g, 192.1 mmol) in dichloromethane (1500 ml) under argon atmosphere was added 2,3-dihydro-furan (29.1 ml, 26.9 g, 384.1 mmol) and a catalytic amount of p-toluenesulfonic acid monohydrate (1.94 g, 19.2 mmol). The reaction mixture was stirred at reflux for 7 hours, filtered and concentrated. The residue was triturated with hexane, filtered and the solid dried in vacuo. Yield: 70.0 g of 1-methoxy-4-{(tetrahydro-furan-2-yloxy)-[2-(2,4,6-trimethyl-phenyl)acetyl]-amino}-piperidine-4-carboxylic acid methyl ester (compound P3ii.6) as a solid, mp 107-109° C. This material was used without further purification in the next step.

후처리

  1. temperatureat reflux for 7 hours
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customThe residue was triturated with hexane
  5. filtrationfiltered
  6. customthe solid dried in vacuo
  7. customThis material was used without further purification in the next step

출처 및 근거

ORD 기록
ord-7594271058ec47179f730815a600e655
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018135B2

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