POTASSIUM DIPHOSPHATE → 2-(4-(Pyrazin-2-yl)phenyl)acetic acid

HRID 474141笔记

反应方程式

HRID 474141 反应方程式
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:11][CH:10]=2)O1.I[C:21]1[CH:26]=[N:25][CH:24]=[CH:23][N:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[N:22]1[CH:23]=[CH:24][N:25]=[CH:26][C:21]=1[C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:13][CH:14]=1

参与物

7

反应物 3

HCID 62657POTASSIUM DIPHOSPHATEHCID 6428412-碘吡嗪HCID 37190024-(羧甲基)苯基硼酸频那醇酯

产物 1

HCID 595359382-(4-(Pyrazin-2-yl)phenyl)acetic acid收率 32%

试剂、催化剂与溶剂 3

HCID 75806三环己基膦催化剂HCID 9811564三(二亚苄基丙酮)二钯催化剂HCID 312751,4-二氧六环溶剂

实验过程

To a solution of 0.40 g (1.53 mmol) of [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetic acid in 4.0 ml of dioxane was added 0.18 mL (1.73 mmol) of 2-iodopyrazine, 10.3 mg (0.037 mmol) of tricyclohexylphosphine, 13.9 mg (0.015 mmol) of Pd2(dba)3, and 2.0 ml (1.27 M, 2.59 mmol) of aqueous potassium phosphate solution. The resulting suspension was degassed for 10 mins. After 30 min in the microwave at 150° C., the reaction mixture was cooled, acidified with 1N HCl, extracted with ethyl acetate, and washed with brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18) afforded 0.10 g (32%) of (4-pyrazin-2-ylphenyl)acetic acid. 1H NMR (CD3OD, 400 MHz) 9.1 (s, 1H); 8.66 (t, J=1.74 Hz, 1H); 8.51 (d, J=2.57 Hz, 1H); 8.04 (d, J=8.15 Hz, 2H); 7.46 (d, J=8.15 Hz, 2H); 3.70 (s, 2H). ES-MS M+1=215.1.

后处理

  1. customThe resulting suspension was degassed for 10 mins
  2. temperaturethe reaction mixture was cooled
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification
  9. additionby preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18)

来源与证据

ORD记录
ord-cec6615b53614e45a6d4766dc3e42e06
来源数据集
uspto-grants-2014_01
专利号
US08637513B2

反应笔记

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