Water → (+/-)-trans-3-[5-(4-Benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-4-methoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1971883ノート

反応式

HRID 1971883 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][OH:14])[C@H:10]([CH2:15][O:16][C:17]2[N:18]=[N:19][C:20]([CH2:37][CH2:38][CH2:39][CH3:40])=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:25][CH:24]=3)[CH:22]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:43]I.O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][O:14][CH3:43])[C@H:10]([CH2:15][O:16][C:17]2[N:18]=[N:19][C:20]([CH2:37][CH2:38][CH2:39][CH3:40])=[C:21]([C:23]3[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:27][CH:28]=3)[CH:22]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86657770(+/-)-trans-3-[5-(4-Benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-4-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 86657775(+/-)-trans-3-[5-(4-Benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-4-methoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred solution of (±)-trans-3-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-4-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (Example 6, 1.0 mmol, 547 mg) in THF (4.0 mL) at 0° C., NaH (60% dispersion in mineral oil, 1.5 mmol, 60 mg) was added and stirring continued for 10 min at room temperature, then methyl iodide (1.5 mmol, 94 μL) was added. The resulting mixture was stirred at room temperature for 2 hour, poured into water, and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The product was purified by column chromatography using 50% ethyl acetate in hexanes to give (±)-trans-3-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-4-methoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester, which was dissolved in dichloromethane (1.0 mL), added 4.0 M HCl in dioxane (1.0 mL) and stirred at room temperature for 1 hour. Solvents were evaporated to give (±)-trans-4-(4-benzyloxy-phenyl)-3-butyl-6-(4-methoxymethyl-pyrrolidin-3-ylmethoxy)-pyridazine dihydrochloride.

後処理

  1. stirringThe resulting mixture was stirred at room temperature for 2 hour
  2. extractionextracted with ethyl acetate
  3. concentrationconcentrated under reduced pressure
  4. customThe product was purified by column chromatography

出典と根拠

ORDレコード
ord-75b0f1f048ed4b6b8a8f8cf1a0431ed3
出典データセット
uspto-grants-2013_04
特許番号
US08431575B2

反応ノート

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