1,3-Dibromopropane → 1-(4-Bromo-2-fluorophenyl)cyclobutanecarbonitrile

HRID 858691ノート

反応式

HRID 858691 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[C:4]([F:11])[CH:3]=1.Br[CH2:13][CH2:14][CH2:15]Br.[H-].[Na+].[Cl-].[NH4+]>CCOCC.CS(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:9]#[N:10])[CH2:15][CH2:14][CH2:13]2)=[C:4]([F:11])[CH:3]=1

参加物

7

反応物 4

HCID 80011,3-DibromopropaneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 71723082-(4-Bromo-2-fluorophenyl)acetonitrile

生成物 1

HCID 587626531-(4-Bromo-2-fluorophenyl)cyclobutanecarbonitrile収率 59.1%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 3283Diethyl Ether溶媒

実験手順

A solution of (4-bromo-2-fluoro-phenyl)-acetonitrile (4.0 g, 18.7 mmol) from step 1 and 1,3-dibromopropane (2.1 mL, 20.6 mmol) in Et2O (5 mL) was slowly added to a slurry of NaH (1.64 g, 41.1 mmol, 60% in mineral oil) in DMSO (19 mL) at room temperature, being careful to keep the temperature below 35 degrees Celsius. The reaction was stirred for 2.5 hours, and then poured into 150 mL of saturated ammonium chloride. To this mixture was added CH22Cl2, and the layers were separated. The aqueous layer was extracted with 2×50 mL of CH2Cl2, and the organic layers were combined. After drying the liquid over MgSO4, the solids were filtered away, and the organic was concentrated to an oil. It was further purified by flash chromatography (90 g SiO2, 1:99->1:20 (EtOAc/Hexanes) to give the desired product (2.81 g, 59%). 1H NMR (400 MHz, CDCl3) δ: 2.06–2.16 (m, H), 2.51–2.63 (m, H), 2.66–2.76 (qd, J=9347 Hz, 2H), 2.86–2.94 (m, 2H), 7.16–7.22 (t, J=8.21 Hz, H), 7.30–7.41 (m, 2H).

後処理

  1. customthe temperature below 35 degrees Celsius
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with 2×50 mL of CH2Cl2
  4. dry with materialAfter drying the liquid over MgSO4
  5. filtrationthe solids were filtered away
  6. concentrationthe organic was concentrated to an oil
  7. customIt was further purified by flash chromatography (90 g SiO2, 1:99->1:20 (EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-8b6f5a8b663c43a795d6e60f50c5afa2
出典データセット
uspto-grants-2006_12
特許番号
US07148226B2

反応ノート

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