Trimethyl borate → Cyclopropyl-(4-hydroxymethyl-piperidin-1-yl)-methanone

HRID 5138

反応式

HRID 5138 の反応式
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][CH:9]([C:12](OCC)=[O:13])[CH2:8][CH2:7]2)=[O:5])[CH2:3][CH2:2]1.[BH4-].[Li+].B(OC)(OC)OC>O1CCCC1.O>[CH:1]1([C:4]([N:6]2[CH2:7][CH2:8][CH:9]([CH2:12][OH:13])[CH2:10][CH2:11]2)=[O:5])[CH2:2][CH2:3]1

参加物

6

反応物 3

HCID 8470Trimethyl borateHCID 4148881Lithium borohydrideHCID 10036613Ethyl 1-(cyclopropylcarbonyl)piperidine-4-carboxylate

生成物 1

HCID 10012597Cyclopropyl-(4-hydroxymethyl-piperidin-1-yl)-methanone収率 63.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of 1-(cyclopropylcarbonyl)-4-carboethoxy piperidine (35 g, 156 mmol) in anhydrous tetrahydrofuran (350 mL) was stirred at ambient temperature under a nitrogen atmosphere. A solution of lithium borohydride in tetrahydrofuran (2M, 78 mL, 156 mmol) was added dropwise. Trimethyl borate (1.77 mL, 15.7 mmol) was added, then the reduction mixture was stirred for about 48 hours. Water was added dropwise with vigorous stirring until the vigorous gas evolution ceased. The mixture was diluted twofold with water and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. Vacuum distillation (bp 165° C., 0.5 mm Hg) gave a clear, colorless liquid (18.2 g): IR (neat): 3410 (br, s), 3094 (w), 3008 (s), 2918 (s), 2858 (s), 1738 (m), 1613 (s), 1448 (s), 1375 (s), 1316 (s); 1H-NMR: 4.7-4.5 (m, 1H), 4.4-4.1 (m, 1H), 3.6-3.4 (m, 2H), 3.2-2.5 (m, 3H), 2.0-1.7 (m, 4H), 1.4-1.1 (m, 1H), 1.0-0.8 (m, 2H), 0.8-0.65 (m, 2H); HRMS: Calcd for C10H17NO2 :183.1259; Found: 183.1250; Anal.: Calcd for C10H17NO2 :C, 65.54, H, 9.35, N, 7.64; Found: C, 65.83, H, 9.43, N, 7.50.

後処理

  1. stirringwith vigorous stirring until the vigorous gas evolution
  2. extractionextracted three times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. distillationVacuum distillation (bp 165° C., 0.5 mm Hg)

出典と根拠

ORDレコード
ord-832f1035ccee4e16b54fec29013e82eb
出典データセット
uspto-grants-1993_09
特許番号
US05243048

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