Diisopropylamine → 7-Methoxy-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole

HRID 1506454노트

반응식

HRID 1506454 반응식
C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)/[C:29](=[N:33]/[OH:34])/[CH2:28][CH2:27][CH2:26]2.[C:35]1([C:41]2[O:45][N:44]=[C:43]([C:46](OC)=O)[C:42]=2[C:50]([F:53])([F:52])[F:51])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.S(Cl)(Cl)=O>C1COCC1.C(OCC)(=O)C.N1C=CC=CC=1>[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29]1=[N:33][O:34][C:46]([C:43]3[C:42]([C:50]([F:51])([F:52])[F:53])=[C:41]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[O:45][N:44]=3)=[C:28]1[CH2:27][CH2:26]2

참가 물질

10

반응물 6

HCID 7912DiisopropylamineHCID 24386Thionyl ChlorideHCID 2724682Lithium diisopropylamideHCID 6304077N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylidene)hydroxylamineHCID 67168162HCID 67168162, 화합물HCID 178418339Butyllithium

생성물 1

HCID 671716707-Methoxy-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole수율 100%

시약·촉매·용매 3

HCID 1049Pyridine용매HCID 8028Tetrahydrofuran용매3회HCID 8857Ethyl Acetate용매

실험 절차

To a fresh solution of lithium diisopropylamide made by adding butyllithium (6.64 mL, 16.6 mmol) to a stirred mixture of diisopropylamine (2.33 mL, 16.6 mmol) in THF (10 mL) at 0° C. was added a solution of (E)-6-methoxy-3,4-dihydronaphthalen-1(2H)-one oxime (I-2, 1.06 g, 5.53 mmol) in THF (4 mL) over 2 minutes. After complete addition, the reaction mixture turned orange-colored and was stirred for an additional 20 minutes. Methyl 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylate (I-5, 1.00 g, 3.69 mmol) in THF (4 mL) was then added over 5 minutes. The resulting reaction mixture turned dark brown and was stirred for thirty minutes at 0° C. The reaction mixture was allowed to warm to room temperature, quenched with conc. sulfuric acid (1.0 mL), and concentrated under vacuum. The residue was taken up in toluene (25 mL), filtered, and dried. To the filtrate was added pyridine (1.5 mL) and thionyl chloride (0.234 mL, 3.20 mmol), and the reaction mixture was heated at 110° C. for about 20 minutes. The residue was taken up in ethyl acetate (50 mL), stirred, and filtered. The filtrate was concentrated in vacuo to give a dark brown crude product mixture. This crude product was chromatographed on silica gel eluting with a 10% mixture of ethyl acetate in hexane to give 7-Methoxy-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (416 mg, 3.69 mmol, 27%) as a yellowish solid. The product had an HPLC ret. time=4.32 min (condition B). LC/MS M+1=413.15.

후처리

  1. additionAfter complete addition
  2. customThe resulting reaction mixture
  3. stirringwas stirred for thirty minutes at 0° C
  4. customquenched with conc. sulfuric acid (1.0 mL)
  5. concentrationconcentrated under vacuum
  6. filtrationfiltered
  7. customdried
  8. temperaturethe reaction mixture was heated at 110° C. for about 20 minutes
  9. stirringstirred
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated in vacuo
  12. customto give a dark brown crude product mixture
  13. customThis crude product was chromatographed on silica gel eluting with a 10% mixture of ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-fc8241c99cf341a4bae2b0e23a0acd65
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216972B2

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