Hydrochloric Acid → 4-(1-Cyanocyclobutyl)benzonitrile

HRID 603113

反応式

HRID 603113 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH:11]1([C:15]#[N:16])[CH2:14][CH2:13][CH2:12]1.F[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1.Cl>C1COCC1>[C:15]([C:11]1([C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)[CH2:14][CH2:13][CH2:12]1)#[N:16]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 145174-FluorobenzonitrileHCID 78148CyanocyclobutaneHCID 3251421Potassium bis(trimethylsilyl)amide

生成物 1

HCID 582984874-(1-Cyanocyclobutyl)benzonitrile収率 55.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

Solid KHMDS (3.48 g, 17.5 mmol) is dissolved in THF (20.0 mL) and cooled to 0° C. Cyclobutanecarbonitrile (1.42 g, 17.5 mmol) is added, and the resulting solution stirred for 40 minutes. A solution of 4-fluorobenzonitrile (2.12 g, 17.5 mmol) in THF (10.0 mL) is added, and the mixture stirred for 2 hours at 0° C. 1N HCl (50.0 mL) is added to the reaction mixture and the aqueous phase extracted with EtOAc (4×40.0 mL). The combined organic phases are dried over MgSO4, filtered and concentrated on the rotovaporator. The product is purified by flash chromatography (CombiFlash), eluting with mixtures of heptanes and EtOAc (0% EtOAc to 40% EtOAc) to yield the desired product (1.76 g, 9.67 mmol, 55%). 1H NMR (400 MHz, DMSO-D6) ε ppm 1.92-2.12 (m, 1H) 2.19-2.37 (m, 1H) 2.57-2.69 (m, 2H) 2.71-2.82 (m, 2H) 7.67 (d, J=8.59 Hz, 2H) 7.91 (d, J=8.79 Hz, 2H).

後処理

  1. stirringthe mixture stirred for 2 hours at 0° C
  2. extractionthe aqueous phase extracted with EtOAc (4×40.0 mL)
  3. dry with materialThe combined organic phases are dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated on the rotovaporator
  6. customThe product is purified by flash chromatography (CombiFlash)
  7. washeluting with mixtures of heptanes and EtOAc (0% EtOAc to 40% EtOAc)

出典と根拠

ORDレコード
ord-84ebabcd9ce14158bac68c778d9469e3
出典データセット
uspto-grants-2011_03
特許番号
US07906654B2

関連ノート

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