Hydrochloric Acid → Methyl 4-(4-fluorophenyl)-6-isopropyl-1H-pyrrolo[2,3-B]pyridine-5-carboxylate

HRID 892870노트

반응식

HRID 892870 반응식
[Br-].[CH3:2]OC[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[NH2-].[Na+].[NH2:26][C:27]1[C:32]([CH:33]=O)=[C:31]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)[C:30]([C:42]([O:44][CH3:45])=[O:43])=[C:29]([CH:46]([CH3:48])[CH3:47])[N:28]=1.[Br-].COC[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[NH2-].[Na+].Cl.[OH-].[Na+]>O1CCCC1>[F:41][C:38]1[CH:39]=[CH:40][C:35]([C:31]2[C:30]([C:42]([O:44][CH3:45])=[O:43])=[C:29]([CH:46]([CH3:47])[CH3:48])[N:28]=[C:27]3[NH:26][CH:2]=[CH:33][C:32]=23)=[CH:36][CH:37]=1

참가 물질

8

반응물 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24533Sodium amideHCID 2773654(Methoxymethyl)triphenylphosphonium bromideHCID 11438468HCID 11438468, 화합물HCID 71311430HCID 71311430, 화합물

생성물 1

HCID 14994382Methyl 4-(4-fluorophenyl)-6-isopropyl-1H-pyrrolo[2,3-B]pyridine-5-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

23.9 g (55 mmol) of a mixture of methoxymethyltriphenylphosphonium bromide and sodium amide are covered with a layer of 145 ml of anhydrous tetrahydrofuran and the mixture is stirred vigorously for 15 min. 17.4 g (55 mmol) of the compound from Example V are added to 145 ml of tetrahydrofuran and the mixture is stirred at room temperature for 1 h. A further 23.9 g (55 mmol) of methoxymethyltriphenylphosphonium bromide/sodium amide are added and the mixture is stirred at room temperature for 60 min. 185 ml (1.11 mol) of 6 M hydrochloric acid are added, and the mixture is heated to reflux for 1 h and cooled. It is neutralized using 5 M sodium hydroxide solution and the phases are separated. The aqueous phase is extracted twice with ethyl acetate, and the combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated to dryness. The residue which remains is dissolved in dichloromethane and added to a glass frit (porosity 3) which contains 450 g of silica gel 230-400 mesh. The mixture is eluted without sucking dry using a gradient of petroleum ether/ethyl acetate of 4:1 to 2:1. The eluate is concentrated to dryness in vacuo and the residue is thoroughly stirred in a mixture of ether/petroleum ether. Yield: 13.8 g (80% of theory) of colorless crystals M.p.: 187° C.

후처리

  1. stirringthe mixture is stirred at room temperature for 1 h
  2. stirringthe mixture is stirred at room temperature for 60 min
  3. temperaturethe mixture is heated
  4. temperatureto reflux for 1 h
  5. temperaturecooled
  6. customthe phases are separated
  7. extractionThe aqueous phase is extracted twice with ethyl acetate
  8. washthe combined organic phases are washed with saturated sodium chloride solution
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated to dryness
  11. dissolutionThe residue which remains is dissolved in dichloromethane
  12. additionadded to a glass frit (porosity 3) which
  13. washThe mixture is eluted
  14. customwithout sucking dry
  15. concentrationThe eluate is concentrated to dryness in vacuo
  16. stirringthe residue is thoroughly stirred in a mixture of ether/petroleum ether

출처 및 근거

ORD 기록
ord-8b8c8b27345d486abdb171488f371a87
출처 데이터셋
uspto-grants-1992_06
특허 번호
US05120782

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