Chloroform → 5-(Hydroxymethyl)nicotinonitrile

HRID 359680ノート

反応式

HRID 359680 の反応式
[OH:1][CH2:2][C:3]1[CH:4]=[C:5](Br)[CH:6]=[N:7][CH:8]=1.[Cu][C:11]#[N:12].C(Cl)(Cl)Cl>N1C=CC=CC=1.[OH-].[NH4+].[Cl-].[NH4+]>[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:11]#[N:12])[CH:6]=[N:7][CH:8]=1

参加物

7

反応物 3

HCID 6212ChloroformHCID 2784733(5-Bromo-3-pyridinyl)methanolHCID 178418546HCID 178418546、化合物

生成物 1

HCID 224165405-(Hydroxymethyl)nicotinonitrile収率 357.5%

試薬・触媒・溶媒 3

HCID 1049Pyridine溶媒HCID 14923Ammonium Hydroxide溶媒HCID 25517Ammonium Chloride溶媒

反応条件

温度
165 °C

実験手順

A stirred mixture of 5-hydroxymethyl-3-bromopyridine (8.50 g, 45.2 mmol) and copper (I) cyanide (10.1 g, 11.3 mmol) in pyridine (50 mL) was heated in a sealed pressure reaction vessel at 165° C. for 20 hours. After cooling to 23° C., the mixture was diluted with concentrated ammonium hydroxide (15 mL) and saturated aqueous ammonium chloride (60 mL), after stirring for 2 hours, the mixture was treated with chloroform (50 mL) and allowed to set for 72 hours. The aqueous layer was then extracted with chloroform. The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 2 inch column, 4:1 EtOAc:hexane as eluant) followed by crystallization from diethyl ether to afford 5-hydroxymethyl-3-pyridinecarbonitrile (5.42 g, 40.4 mmol, 89% yield): Rf 0.49 (EtOAc); 1H NMR (CDCl3, 200 MHz)δ8.80 (m, 2H), 8.03 (s, 1H), 4.83 (s, 2H).

後処理

  1. temperatureAfter cooling to 23° C.
  2. waitto set for 72 hours
  3. extractionThe aqueous layer was then extracted with chloroform
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (silica gel, 2 inch column, 4:1 EtOAc:hexane as eluant)
  8. customfollowed by crystallization from diethyl ether

出典と根拠

ORDレコード
ord-eb2d65ebfb204e508210ae122fbd8280
出典データセット
uspto-grants-1991_03
特許番号
US05002949

反応ノート

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