Potassium Iodide → HCID 11555972, 화합물

HRID 1785960노트

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HRID 1785960 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C@H:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]([C:22]([C:24]3[CH:25]=NN(C(C)C)C=3)=[O:23])[C@@H:14]([CH3:32])[CH2:13]2)[C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.[CH:33](N1C=[C:39]([C:41]([Cl:43])=[O:42])[CH:38]=N1)(C)C.Br[CH2:45][CH2:46][C:47]([CH3:54])([CH3:53])[C:48]([O:50][CH2:51][CH3:52])=[O:49].[C:55](=[O:58])([O-:57])[O-:56].[K+].[K+].[I-].[K+].C[N:64]([CH:66]=[O:67])C>O>[C:9]([N:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[C@H:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([C:22]([C:24]2[O:42][N:64]=[C:66]([O:67][CH2:45][CH2:46][C:47]([CH3:54])([CH3:53])[C:48]([O:50][CH2:51][CH3:52])=[O:49])[CH:25]=2)=[O:23])[C@@H:14]([CH3:32])[CH2:13]1)(=[O:11])[CH3:10].[Cl:43][C:41]([C:39]1[O:56][N:64]=[C:66]([O:67][CH2:45][CH2:46][C:47]([CH3:54])([CH3:53])[C:48]([O:50][CH2:51][CH3:52])=[O:49])[CH:38]=1)=[O:42].[CH2:51]([O:50][C:48](=[O:49])[C:47]([CH3:54])([CH3:53])[CH2:46][CH2:45][O:67][C:66]1[CH:10]=[C:9]([C:55]([O:57][CH3:33])=[O:58])[O:11][N:64]=1)[CH3:52]

참가 물질

10

반응물 6

HCID 4875Potassium IodideHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11510715HCID 11510715, 화합물HCID 14536789Ethyl 4-bromo-2,2-dimethylbutanoateHCID 60136483HCID 60136483, 화합물

생성물 3

HCID 11555972HCID 11555972, 화합물HCID 68918373HCID 68918373, 화합물HCID 87623728HCID 87623728, 화합물

시약·촉매·용매 1

HCID 962Water용매

실험 절차

Ethyl 4-[(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}isoxazol-3-yl)oxy]-2,2-dimethylbutanoate was prepared following the procedure for N-(4-chlorophenyl)-N-{(2S,4R)-1-[(1-isopropyl-1H-pyrazol-4-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide, substituting ethyl 4-{[5-(chlorocarbonyl)isoxazol-3-yl]oxy}-2,2-dimethylbutanoate for 1-isopropyl-1H-pyrazole-4-carbonyl chloride. (Ethyl 4-{[5-(chlorocarbonyl)isoxazol-3-yl]oxy}-2,2-dimethylbutanoate was prepared in three steps from methyl 3-hydroxy 5-isoxazole carboxylate. Methyl 3-hydroxy 5-isoxazole carboxylate (1.00 g, 6.94 mmol) was alkylated using ethyl 4-bromo-2,2-dimethylbutanoate (1.59 g, 7.63 mmol) in the presence of potassium carbonate (1.05 g, 7.64 mmol) and catalytic potassium iodide in DMF (5.00 mL) at room temperature overnight. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organics were washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated in vacuo and purified on silica gel by flash chromatography using hexane/ethyl acetate (10-50% gradient) to afford methyl 3-(4-ethoxy-3,3-dimethyl-4-oxobutoxy)isoxazole-5-carboxylate in 35% yield. Selective hydrolysis of the methyl ester by subsequent treatment with lithium hydroxide (aq) (1.50 equiv.) in methanol at room temperature afforded 3-(4-ethoxy-3,3-dimethyl-4-oxobutoxy)isoxazole-5-carboxylic acid which was then treated with oxalyl chloride and catalytic DMF in dichloromethane to yield the desired ethyl 4-{[5-(chlorocarbonyl)isoxazol-3-yl]oxy}-2,2-dimethylbutanoate).

후처리

  1. customat room temperature
  2. customovernight
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organics were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified on silica gel by flash chromatography

출처 및 근거

ORD 기록
ord-a9da0719d6ca484cbe4fa7c148a5d084
출처 데이터셋
uspto-grants-2009_03
특허 번호
US07504508B2

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