Sulfuric acid magnesium salt (1:1) → Ethyl 2-(Trifluoromethyl)-7-(triphenylmethyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxylate

HRID 132856노트

반응식

HRID 132856 반응식
[C:1]([N:20]1CCCC(=O)[CH2:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S([O-])([O-])(=O)=O.[Mg+2].[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.C(O[CH:41]=[C:42]([C:48](=O)[C:49]([F:52])([F:51])[F:50])[C:43]([O:45][CH2:46][CH3:47])=[O:44])C.C([O-])(=O)C.[NH4+]>O1CCCC1>[F:50][C:49]([F:51])([F:52])[C:48]1[C:42]([C:43]([O:45][CH2:46][CH3:47])=[O:44])=[CH:41][C:36]2[CH2:35][CH2:34][N:20]([C:1]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:21][C:37]=2[N:33]=1

참가 물질

7

반응물 5

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 31268PyrrolidineHCID 517165Ammonium AcetateHCID 4685753Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoateHCID 227070511-Tritylpiperidin-3-one

생성물 1

HCID 69222993Ethyl 2-(Trifluoromethyl)-7-(triphenylmethyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of N-trityl-3-piperidone (1.22 g, 3.6 mmol), magnesium sulfate (2.70 g) and pyrrolidine (0.36 mL, 4.3 mmol) in 10 mL of tetrahydrofuran was stirred at room temperature for 72 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resultant crude enamine was dissolved in 15 mL of dry dioxane, cooled to approximately 10° C. and treated dropwise with ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate (0.77 mL, 3.9 mmol). The resultant red-orange solution was allowed to warm to room temperature overnight. Ammonium acetate (0.61 g) was added to the blood-red solution, and the mixture was heated at reflux for 3 h, cooled to room temperature and concentrated under reduced pressure. The residue was stirred with 100 mL of dry ether, filtered through a pad of Celite, and concentrated under reduced pressure. The resultant dark red gum was purified by flash chromatography (silica gel; 5% ethyl acetate/hexanes as eluant) to afford the title compound as a light orange foam.

후처리

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. dissolutionThe resultant crude enamine was dissolved in 15 mL of dry dioxane
  4. temperaturecooled to approximately 10° C.
  5. temperatureto warm to room temperature overnight
  6. temperaturethe mixture was heated
  7. temperatureat reflux for 3 h
  8. temperaturecooled to room temperature
  9. concentrationconcentrated under reduced pressure
  10. stirringThe residue was stirred with 100 mL of dry ether
  11. filtrationfiltered through a pad of Celite
  12. concentrationconcentrated under reduced pressure
  13. customThe resultant dark red gum was purified by flash chromatography (silica gel; 5% ethyl acetate/hexanes as eluant)

출처 및 근거

ORD 기록
ord-43bf468a9b5f4ee19839603d092becd8
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388019B2

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