Oxazole → Methyl 4-butyl-8-(1,3-oxazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

HRID 14188

반응식

HRID 14188 반응식
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[CH2:11]([N:15]1[C:20]2[CH:21]=[C:22]([C:26]([O:28][CH2:29]C)=[O:27])[CH:23]=[C:24](I)[C:19]=2[O:18][CH2:17][CH2:16]1)[CH2:12][CH2:13][CH3:14]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH2:11]([N:15]1[C:20]2[CH:21]=[C:22]([C:26]([O:28][CH3:29])=[O:27])[CH:23]=[C:24]([C:2]3[O:1][CH:5]=[CH:4][N:3]=3)[C:19]=2[O:18][CH2:17][CH2:16]1)[CH2:12][CH2:13][CH3:14]

참가 물질

7

반응물 3

HCID 9255OxazoleHCID 21086105ethyl 4-butyl-8-iodo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 21086201Methyl 4-butyl-8-(1,3-oxazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate수율 71.7%

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
-70 °C

실험 절차

To a −70° C. solution of oxazole (227 mg) in tetrahydrofuran (10 mL) was added n-butyllithium (2.5 M in hexanes, 2 mL). After stirred at −70° C. for 30 min, zinc chloride (1 M in ethyl ether, 13 mL) was added. The mixture was warmed to 0° C. for 1 h. To this mixture was then added ethyl 4-butyl-8-iodo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (600 mg, 1.6 mmol) in THF (5 mL) followed by tetrakis triphenylphosphine palladium(0) (115 mg). The mixture was heated at reflux for 3 h, diluted with ethyl acetate (300 mL) and washed with water followed by brine. The organic solution was dried (sodium sulfate) and concentrated under reduced pressure. Purification by silica gel plug (1:1 acetate/hexanes) provided 363 mg of the title compound: 1H NMR (300 MHz, CDCl3) δ 7.96, 7.73, 7.40, 7.28, 4.44, 3.90, 3.43, 3.34, 1.61, 1.41, 0.98.

후처리

  1. temperatureThe mixture was warmed to 0° C. for 1 h
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 3 h
  4. washwashed with water
  5. dry with materialThe organic solution was dried (sodium sulfate)
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel plug (1:1 acetate/hexanes)

출처 및 근거

ORD 기록
ord-89e7e13a6e064a79961c44e05570b1e8
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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