Potassium Iodide → HCID 11555972, compound

HRID 1785960Notes

Reaction equation

HRID 1785960 reaction equation
[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]

Participants

10

Reactant 6

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

Product 3

HCID 11555972HCID 11555972, compoundHCID 68918373HCID 68918373, compoundHCID 87623728HCID 87623728, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a9da0719d6ca484cbe4fa7c148a5d084
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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