Lithium Carbonate → 6-Fluoro-9-(4-fluorobenzyl)-9H-carbazol-4-ol

HRID 1057632ノート

反応式

HRID 1057632 の反応式
C1C=C[NH+]=CC=1.Br[Br-]Br.[F:10][C:11]1[CH:12]=[C:13]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[C:19]1[CH2:18][CH2:17][CH2:16][C:15](=[O:32])[C:14]2=1.[Br-].[Li+].C(=O)([O-])[O-].[Li+].[Li+]>C1COCC1.CN(C=O)C>[F:10][C:11]1[CH:12]=[C:13]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[C:19]1[CH:18]=[CH:17][CH:16]=[C:15]([OH:32])[C:14]2=1

参加物

6

反応物 3

HCID 11125Lithium CarbonateHCID 82050Lithium BromideHCID 186716586-Fluoro-9-(4-fluorobenzyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one

生成物 1

HCID 186716846-Fluoro-9-(4-fluorobenzyl)-9H-carbazol-4-ol収率 52%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
75 °C

実験手順

Pyridinium bromide perbromide (0.7068 g, 0.0022 mol) is added to a mixture of 6-fluoro-9-(4-fluorobenzyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.5245 g, 0.0017 mol) in THF (4 mL) and DMF (4 mL) and the mixture is heated to 75° C. After stirring for 6.5 h, the mixture is stored in the freezer overnight. Heating is resumed for an additional 2.5 h, at which time THF is removed under reduced pressure and the residue is partitioned between dichloromethane and brine. The combined organic layers are washed with dilute sodium thiosulfate/brine and the aqueous layer is backwashed with dichloromethane. The combined organic layers are dried over sodium sulfate and concentrated under reduced pressure to give a residue. The residue is heated to 120° C. in DMF (8 mL) with lithium bromide (0.3412 g, 0.0039 mol) and lithium carbonate (0.2548 g, 0.0035 mol). After 2 h, DMF is removed under high vacuum and the mixture is partitioned between dichloromethane and water. The combined organic layers are washed with water, dried over sodium sulfate and concentrated to an oil. The oil is chromatographed on silica gel (100 mL) using dichloromethane/hexane (30/70 to 50/50) to give 0.2706 g (52%) of the title compound; MS (ESI−) for C19H13F2NO m/z 308.0 (M−H)−; IR (drift) 1511, 1483, 1465, 1450, 1336, 1222, 1215, 1172, 1157, 1138, 883, 858, 791, 777, 744 cm−1; 1H NMR (CDCl3) δ5.35, 5.44, 6.57, 6.95, 7.06-7.30, 8.01. Anal. Calcd for C19H13F2NO: C, 73.78; H, 4.24; N, 4.53. Found: C, 72.65; H, 4.20; N, 4.45.

後処理

  1. customis stored in the freezer overnight
  2. temperatureHeating
  3. customis removed under reduced pressure
  4. customthe residue is partitioned between dichloromethane and brine
  5. washThe combined organic layers are washed with dilute sodium thiosulfate/brine
  6. dry with materialThe combined organic layers are dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give a residue
  9. waitAfter 2 h
  10. customDMF is removed under high vacuum
  11. customthe mixture is partitioned between dichloromethane and water
  12. washThe combined organic layers are washed with water
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated to an oil
  15. customThe oil is chromatographed on silica gel (100 mL)

出典と根拠

ORDレコード
ord-d91641736fa44681ad882a9ad18c22c5
出典データセット
uspto-grants-2003_02
特許番号
US06514968B1

反応ノート

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