Diethyl Ether → {1-[(5-Cyclopropyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-propyl}-carbamic acid tert-butyl ester

HRID 1455589ノート

反応式

HRID 1455589 の反応式
[CH:1]1([C:4]2[O:5][CH:6]=[N:7][N:8]=2)[CH2:3][CH2:2]1.[Li]CCCC.[Mg+2].[Br-].[Br-].O(CC)CC.[C:22]([O:26][C:27](=[O:34])[NH:28][CH:29]([CH:32]=[O:33])[CH2:30][CH3:31])([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[C:22]([O:26][C:27](=[O:34])[NH:28][CH:29]([CH:32]([C:6]1[O:5][C:4]([CH:1]2[CH2:3][CH2:2]2)=[N:8][N:7]=1)[OH:33])[CH2:30][CH3:31])([CH3:23])([CH3:24])[CH3:25]

参加物

7

反応物 5

HCID 3283Diethyl EtherHCID 82241Magnesium BromideHCID 11286906tert-butyl N-(1-oxobutan-2-yl)carbamateHCID 197768782-Cyclopropyl-1,3,4-oxadiazoleHCID 178418339Butyllithium

生成物 1

HCID 68822601{1-[(5-Cyclopropyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-propyl}-carbamic acid tert-butyl ester収率 49%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

A solution of 2-cyclopropyl-[1,3,4]oxadiazole (2.16 g, 19.6 mmol) in dry THF (100 mL) is cooled to −78° C. nBuLi (1.6M in hexanes, 12.3 mL, 19.6 mmol) is added dropwise. The reaction mixture is stirred at −78° C. for 40 min. MgBr2.OEt2 (5.0692 g, 19.6 mmol) is added. The reaction mixture is allowed to warm up to −45° C. and stirred at that temperature for 1.5 hr. A solution of (1-formyl-propyl)-carbamic acid tert-butyl ester (3.7 g, 19.6 mmol) in THF (40 mL) is added. The reaction mixture is allowed to warm up to −20° C. and stirred at that temperature for 3.5 hrs. The reaction mixture is quenched with a solution of saturated NH4Cl solution and extracted with ethyl acetate. Combined organic extracts is washed with saturated NaCl solution and dried over MgSO4. The solvent is evaporated under reduced pressure and the crude is purified by column chromatography eluting with ethyl acetate and heptane mixture to give {1-[(5-cyclopropyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-propyl}-carbamic acid tert-butyl ester (2.83 g, 49%).

後処理

  1. additionis added dropwise
  2. temperatureto warm up to −45° C.
  3. stirringstirred at that temperature for 1.5 hr
  4. temperatureto warm up to −20° C.
  5. stirringstirred at that temperature for 3.5 hrs
  6. customThe reaction mixture is quenched with a solution of saturated NH4Cl solution
  7. extractionextracted with ethyl acetate
  8. washCombined organic extracts is washed with saturated NaCl solution
  9. dry with materialdried over MgSO4
  10. customThe solvent is evaporated under reduced pressure
  11. customthe crude is purified by column chromatography
  12. washeluting with ethyl acetate and heptane mixture

出典と根拠

ORDレコード
ord-93a97c3767c244b9addf2079da96a648
出典データセット
uspto-grants-2009_01
特許番号
US07482448B2

反応ノート

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