Hydrochloric Acid → (trans)-9-(3-bromo-4-fluorophenyl)-7-methyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione

HRID 478306ノート

反応式

HRID 478306 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:14]([C:15]([O:17]C)=[O:16])=[C:13]([CH3:19])[NH:12][C:11]3[CH2:20][O:21][CH:22]([CH3:25])[C:23](=[O:24])[C:10]2=3)[CH:5]=[CH:6][C:7]=1[F:8].N1C=CC=CC=1.[Br-].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.Cl>C(Cl)(Cl)Cl.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[C:10]3[C:23](=[O:24])[C@@H:22]([CH3:25])[O:21][CH2:20][C:11]=3[NH:12][C:13]3[CH2:19][O:17][C:15](=[O:16])[C:14]2=3)[CH:5]=[CH:6][C:7]=1[F:8]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 18000971methyl 4-(3-bromo-4-fluorophenyl)-2,6-dimethyl-5-oxo-4,5,6,8-tetrahydro-1H-pyrano[3,4-b]pyridine-3-carboxylateHCID 21124087Pyridiniumtribromide

生成物 1

HCID 70003743(trans)-9-(3-bromo-4-fluorophenyl)-7-methyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
-10 °C

実験手順

The product from Example 84D (1.0 g, 2.5 mmol) was dissolved in chloroform (15 mL) under a nitrogen atmosphere, cooled to −10° C., treated with pyridine (0.24 mL, 3.0 mmol) and pyridinium tribromide (0.97 g, 3.0 mmol), stirred at −10° C. for 20 minutes, diluted with dichloromethane (100 mL) and treated with 1M HCl (10 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (50 mL). The combined organic layers were dried (MgSO4), filtered, concentrated, heated to 130° C. under nitrogen for 15 minutes and cooled to ambient temperature. The residue was purified by chromatography on silica gel eluting with 38:1:1:40 ethyl acetate:formic acid:water:hexane to provide the title compound as the faster moving diasteriomer which was crystallized from dichloromethane. 1H NMR (DMSO-d6) δ 1.22 (d, 3H), 4.12 (q, 1H), 4.48 (d, 1H), 4.65 (d, 1H), 4.68 (s, 1H), 4.86 (dd, 1H), 4.99 (d, 1H), 7.24-7.28 (m, 2H), 7.48 (dd, 1H), 10.42 (bs, 1H);

後処理

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with dichloromethane (50 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. temperatureheated to 130° C. under nitrogen for 15 minutes
  7. temperaturecooled to ambient temperature
  8. customThe residue was purified by chromatography on silica gel eluting with 38:1:1:40 ethyl acetate

出典と根拠

ORDレコード
ord-f430aede5dbe4ec79fb847f24686be3f
出典データセット
uspto-grants-2003_11
特許番号
US06642222B2

反応ノート

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