Isopropanol → 1-(3-Fluorophenyl)cyclobutane-1-carbonitrile

HRID 260170

반응식

HRID 260170 반응식
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([CH2:10][C:11]#[N:12])[CH:7]=[CH:8][CH:9]=1.Br[CH2:14][CH2:15][CH2:16]Br.C(O)(C)C>CS(C)=O.CCOCC.O>[F:3][C:4]1[CH:5]=[C:6]([C:10]2([C:11]#[N:12])[CH2:16][CH2:15][CH2:14]2)[CH:7]=[CH:8][CH:9]=1

참가 물질

8

반응물 4

HCID 3776IsopropanolHCID 80011,3-DibromopropaneHCID 24758Sodium hydrideHCID 68145Benzeneacetonitrile, 3-fluoro-

생성물 1

HCID 224027611-(3-Fluorophenyl)cyclobutane-1-carbonitrile수율 57.2%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 3283Diethyl Ether용매

반응 조건

온도
0 °C

실험 절차

CHART B, Preparation of the amine used in Chart B, Step B-2. A stirred suspension of freshly washed and dried sodium hydride (50% by wt, 9.59 g, 200 mmol) in dry dimethyl sulfoxide (75 mL) under N2 is cooled to 0° C. A mixture of 3-fluorophenylacetonitrile (8.6 mL, 74.0 mmol) and 1,3-dibromopropane (8.3 mL, 81.4 mmol) in ether (40 mL) is then added dropwise over 35 minutes, via cannula. The resulting orange-red mixture is allowed to stir at 20°-25° C. overnight. The thick reaction mixture is cooled to 0° C. and treated with isopropanol (4 mL). After stirring for 15 minutes, water (64 mL) is added in 10 mL increments and the phases are separated. The aqueous layer is extracted with ether (4×100 mL). The combined organics are washed with water (3×100mL), brine (1×100 mL), dried (MgSO4), filtered and concentrated. The product is distilled at 95° C. (1.0 torr) to afford 7.41 g of 1-(3-fluorophenyl)cyclobutanecarbonitrile. 1H NMR (CDCl3) δ7.39 (m, 1 H), 7.19 (m, 1 H), 7.13 (m, 1 H), 7.05 (m, 1 H), 2.81 (m, 2 H), 2.60 (m, 4 H), 2.50 (m, 1 H), 2.12 (m, 1 H); 13C NMR (CDCl3) δ164.6, 161.3, 142.2, 130.6, 130.5, 123.8, 121.37, 121.32, 115.0, 114.7, 113.0, 112.7, 77.2, 40.9, 39.9, 34.6, 17.0.

후처리

  1. additionA stirred suspension
  2. washof freshly washed
  3. additionis then added dropwise over 35 minutes, via cannula
  4. stirringAfter stirring for 15 minutes
  5. customthe phases are separated
  6. extractionThe aqueous layer is extracted with ether (4×100 mL)
  7. washThe combined organics are washed with water (3×100mL), brine (1×100 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. distillationThe product is distilled at 95° C. (1.0 torr)

출처 및 근거

ORD 기록
ord-bdae9d71641f4c448acf8139f0fa25a8
출처 데이터셋
uspto-grants-1996_06
특허 번호
US05525742

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