Acetic Acid → (e)-11-(Bromomethylene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepine

HRID 1670594노트

반응식

HRID 1670594 반응식
C(OC(=O)[CH:5]=[C:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][O:9][C:8]2[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:7]1=2)C.[OH-].[Li+].C(O)(=O)C.[Br:29]N1C(=O)CCC1=O>C(O)(C)C.O>[Br:29]/[CH:5]=[C:6]1/[C:7]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:8]=2[O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]/1=2

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 3939Lithium HydroxideHCID 67184N-bromobutanimideHCID 67134827(3-fluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl ester

생성물 1

HCID 59468684(e)-11-(Bromomethylene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepine수율 93.8%

시약·촉매·용매 2

HCID 962Water용매HCID 3776Isopropanol용매

반응 조건

온도
70 °C

실험 절차

To a suspension of (3-fluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl ester (0.23 mol, 69.5 g) in isopropanol (725 mL) add a solution of lithium hydroxide (0.53 mol, 12.0 g) in water (125 mL) and warm to 70° C. for 4 h. Allow the mixture to cool to 40° C. and then treat with glacial acetic acid (0.44 mol, 25 mL). After stirring for 15 min, add N-bromosuccinimide (0.25 mol, 44 g). Bubbling ensues, the temperature rises to 45° C., and solids form after a few min. Stir the mixture at 40-45° C. for one hour and cool to room temperature. Add sodium bisulfite (4.5 g) in water (150 mL), saturated aqueous sodium bicarbonate (150 mL), and water (450 mL). Filter the resulting suspension and rinse with cold 1:1 isopropanol/water (300 mL). Dry the solid at 60° C./20 mm Hg overnight to obtain the title compound (65.8 g, 93%). 1H NMR (400 MHz, DMSO-d6) δ 4.9-5.4 (br d, 2H), 6.63 (dd, 1H), 6.77 (dt, 1H), 7.13 (s, 1H), 7.32-7.46 (m, 4H), 7.52 (dd, 1H).

후처리

  1. temperatureAllow the mixture to cool to 40° C.
  2. customBubbling
  3. customrises to 45° C.
  4. stirringStir the mixture at 40-45° C. for one hour
  5. temperaturecool to room temperature
  6. filtrationFilter the resulting suspension
  7. washrinse with cold 1:1 isopropanol/water (300 mL)
  8. customDry the solid at 60° C./20 mm Hg overnight

출처 및 근거

ORD 기록
ord-33770e04adf94df7896d41ee3356ed3c
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994164B2

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