Acetonitrile → 4,4-Dimethyl-3-oxo-5-(tetrahydro-pyran-2-yloxy)-pentanenitrile

HRID 553616ノート

反応式

HRID 553616 の反応式
CO[C:3](=[O:15])[C:4]([CH3:14])([CH3:13])[CH2:5][O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][O:8]1.[C:16](#[N:18])[CH3:17].[H-].[Na+]>C1(C)C=CC=CC=1>[CH3:14][C:4]([CH3:13])([CH2:5][O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][O:8]1)[C:3](=[O:15])[CH2:17][C:16]#[N:18]

参加物

5

反応物 3

HCID 6342Acetonitrile2 回HCID 24758Sodium hydride2 回HCID 59253280methyl 2,2-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propanoate

生成物 1

HCID 592532944,4-Dimethyl-3-oxo-5-(tetrahydro-pyran-2-yloxy)-pentanenitrile収率 101.4%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

A solution of 129 g (0.60 mol) of 2,2-dimethyl-3-(tetrahydro-pyran-2-yloxy)-propionic acid methyl ester and 44 mL (0.84 mol) of acetonitrile in toluene (250 mL) is added dropwise to the refluxing suspension of 33 g (0.84 mol) of sodium hydride (60% in mineral oil) in toluene (600 mL) over a period of 2 h. After the addition, the reaction mixture is stirred at reflux for 3 h. Additional 16.7 g (0.42 mol) of sodium hydride (60% dispersion in mineral oil) and 22 mL (0.42 mol) of acetonitrile are added to the reaction mixture and the refluxing is continued for another 1.5 h. After this time, the reaction mixture is cooled to room temperature and ice water (˜0.8 L) is added. The layers are separated and the aqueous layer is neutralized to pH ˜6-7 by adding 1M aqueous HCl solution. The aqueous layer is extracted with ethyl acetate (3×0.8 L). The organic layers are combined, washed with brine (1.5 L), dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to yield 137 g of 4,4-dimethyl-3-oxo-5-(tetrahydro-pyran-2-yloxy)-pentanenitrile as a brown oil, which is used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.09 (6H, s), 1.10 (6H, s), 1.4-1.7 (6H, m), 3.3 (1H, m), 3.35 (1H, d), 3.4 (1H, m), 3.6 (1H, d), 3.7 (1H, m), 4.2 (1H, s); 4.55 (1H, t).

後処理

  1. additionAfter the addition
  2. temperatureat reflux for 3 h
  3. customThe layers are separated
  4. additionby adding 1M aqueous HCl solution
  5. extractionThe aqueous layer is extracted with ethyl acetate (3×0.8 L)
  6. washwashed with brine (1.5 L)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated under reduced pressure

出典と根拠

ORDレコード
ord-a6445837d6a34e9686de6b3bb9c65019
出典データセット
uspto-grants-2011_11
特許番号
US08048899B2

反応ノート

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