氯化铵 → 2-Cyclopropyl-6-(2,3-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17453

反应方程式

HRID 17453 反应方程式
Br[C:2]1[C:3]([F:17])=[C:4]2[O:8][C:7]([CH:9]3[CH2:11][CH2:10]3)=[N:6][C:5]2=[C:12]([C:15]#[N:16])[C:13]=1[CH3:14].[F:18][C:19]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH:9]1([C:7]2[O:8][C:4]3[C:5](=[C:12]([C:15]#[N:16])[C:13]([CH3:14])=[C:2]([C:23]4[CH:22]=[CH:21][CH:20]=[C:19]([F:18])[C:24]=4[F:25])[C:3]=3[F:17])[N:6]=2)[CH2:11][CH2:10]1

参与物

8

反应物 4

HCID 25517氯化铵HCID 62657POTASSIUM DIPHOSPHATEHCID 27343332,3-二氟苯硼酸HCID 510414276-Bromo-2-cyclopropyl-7-fluoro-5-methylbenzoxazole-4-carbonitrile

产物 1

HCID 685869922-Cyclopropyl-6-(2,3-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile收率 53%

试剂、催化剂与溶剂 3

HCID 178418397HCID 178418397，化合物催化剂HCID 8857乙酸乙酯溶剂HCID 312751,4-二氧六环溶剂

反应条件

温度
95 °C

实验过程

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (190 mg, 0.64 mmol), 2,3-difluorophenylboronic acid (407 mg, 2.58 mmol) and tripotassium phosphate (274 mg, 1.29 mmol) were dissolved in 1,4-dioxane (6 ml), then at room temperature, tetrakis(triphenylphosphine)palladium(0) (149 mg, 0.13 mmol) was added. The suspension was stirred under nitrogen atmosphere at 95° C. for 86 hours. After cooling to room temperature, the solution was fractionated with ethyl acetate and aqueous saturated ammonium chloride solution. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=9:1) to obtain the entitled compound (111 mg, 53%) as a white solid.

后处理

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted twice with ethyl acetate
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated away
  6. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=9:1)

来源与证据

ORD记录
ord-0103d49164824ac4adb363d831c820eb
来源数据集
uspto-grants-2010_06
专利号
US07737166B2

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