Oxazole → N-Methyl-5-oxazol-2-yl-N-propyl-isophthalamic acid

HRID 14066

反応式

HRID 14066 の反応式
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.I[C:12]1[CH:13]=[C:14]([CH:19]=[C:20]([C:22]([N:24]([CH3:28])[CH2:25][CH2:26][CH3:27])=[O:23])[CH:21]=1)[C:15]([O:17]C)=[O:16].O.[OH-].[Li+]>O1CCCC1.C(OCC)(=O)C.O1CCCC1.CO.O.C(Cl)(Cl)Cl.[Cl-].[Zn+2].[Cl-]>[CH3:28][N:24]([CH2:25][CH2:26][CH3:27])[C:22]([C:20]1[CH:19]=[C:14]([CH:13]=[C:12]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)[CH:21]=1)[C:15]([OH:17])=[O:16])=[O:23]

参加物

10

反応物 4

HCID 9255OxazoleHCID 168937Lithium hydroxide, monohydrateHCID 21086185Methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoateHCID 178418339Butyllithium

生成物 1

HCID 21085840N-Methyl-5-oxazol-2-yl-N-propyl-isophthalamic acid

試薬・触媒・溶媒 5

HCID 3007855Zincchloride触媒HCID 6212Chloroform溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 21892291Methanol tetrahydrofuran water溶媒

反応条件

温度
0 °C

実験手順

To a −70° C. stirred solution of oxazole (330 mg, 4.8 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 3.3 mL, 5.3 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 14.5 mL, 14.5 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is added a solution of methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoate (1.6 g, 4.5 mmol) in anhydrous tetrahydrofuran (3 mL) followed by palladium(0)tetrakis(triphenylphosphine) (221 mg, 0.19 mmol). The reaction mixture is heated at reflux for 2 h. The reaction mixture is cooled, diluted with ethyl acetate, washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides a solid. The solid is redissolved in 1:1:1 tetrahydrofuran/methanol/water (9 mL), and lithium hydroxide monohydrate (311 mg, 7.4 mmol) is added and stirred 2 h at room temperature. The reaction is diluted in chloroform and washed with 1N hydrochloric acid (aq), water, and brine, dried (sodium sulfate), filtered and concentrated under reduced pressure to give the title compound. ESI MS m/z 287.3 [M−H]−.

後処理

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 2 h
  3. temperatureThe reaction mixture is cooled
  4. washwashed with water, and brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)
  9. customprovides a solid
  10. additionis added
  11. washwashed with 1N hydrochloric acid (aq), water, and brine
  12. dry with materialdried (sodium sulfate)
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-d945e176239c4c6c9e6013b66b49819e
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

関連ノート

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