Benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate → Benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate

HRID 73559ノート

反応式

HRID 73559 の反応式
[CH3:1][Mg]Br.[CH2:4]([O:6][P:7]([N:12]1[CH:18]2[CH:13]1[CH2:14][CH2:15][N:16]([C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[CH2:17]2)([O:9][CH2:10][CH3:11])=[O:8])[CH3:5]>C1COCC1.[Cu]I>[CH2:4]([O:6][P:7]([NH:12][CH:18]1[CH:13]([CH3:1])[CH2:14][CH2:15][N:16]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:17]1)([O:9][CH2:10][CH3:11])=[O:8])[CH3:5]

参加物

5

反応物 2

HCID 59455678Benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylateHCID 178418573HCID 178418573、化合物

生成物 1

HCID 60205257Benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate収率 35%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
10 °C

実験手順

To a suspension of CuI (0.3 equiv.) in anhydrous THF (0.1M) was added methyl magnesium bromide (3M solution in Et2O, 10 equiv.) at −40° C. The reaction was stirred for 30 min, followed by addition of benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate (1.0 equiv.) in THF (0.1M) at −40° C. Allowed the reaction to warm to 10° C. over 5 h, then quenched with water and extracted with ethyl acetate. The organic phase was concentrated under vacuo and purified via silica gel column chromatography eluting with ethyl acetate and hexanes (50% to 100% ethyl acetate) to yield benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate in 35% yield. LCMS (m/z): 385.0 (MH+), Rt=3.38 min.

後処理

  1. customAllowed the reaction
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. concentrationThe organic phase was concentrated under vacuo
  5. custompurified via silica gel column chromatography
  6. washeluting with ethyl acetate and hexanes (50% to 100% ethyl acetate)

出典と根拠

ORDレコード
ord-0db8e0a420254cecb1c79e6ff76e14c6
出典データセット
uspto-grants-2014_09
特許番号
US08829193B2

反応ノート

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