Реакция #467181

ord-57fa8a56fc5f40a5ba86f6c4c8cea0aa

Уравнение реакции

C[C@H](Oc1ccc(B(O)O)cc1)[C@H](O)CCc1cccnc1
(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid
C[C@H](Oc1ccc(B(O)O)cc1)[C@H](O)CCc1cccnc1
(1S,2R)-4-(2-Hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid
N#Cc1cc(Br)ccc1F
3-cyano-4-flurobromobenzene
O=C([O-])[O-].[Na+].[Na+]
sodium carbonate
→
C[C@H](Oc1ccc(-c2ccc(F)c(C#N)c2)cc1)[C@H](O)CCc1cccnc1
title compound
C[C@H](Oc1ccc(-c2ccc(F)c(C#N)c2)cc1)[C@H](O)CCc1cccnc1
(1S,2R)-4-Fluoro-4′-(2-hydroxy-1-methyl-4-pyridin-3-yl-butoxy)biphenyl-3-carbonitrile

Реактанты

C[C@H](Oc1ccc(B(O)O)cc1)[C@H](O)CCc1cccnc1
(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid
C[C@H](Oc1ccc(B(O)O)cc1)[C@H](O)CCc1cccnc1
(1S,2R)-4-(2-Hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid
N#Cc1cc(Br)ccc1F
3-cyano-4-flurobromobenzene
O=C([O-])[O-].[Na+].[Na+]
sodium carbonate

Реагенты

c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
tetrakis(triphenylphosphine)palladium

Растворители

CCO
ethanol

Условия реакции

Температура
80°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    ДругоеPrepared
  2. 2
    ДругоеAfter work-up, the residue was purified by normal-phase HPLC
  3. 3
    Промывкаeluting a gradient of 0-10% ethanol in dichloromethane

Методика

Prepared according to the method described in Example 12 from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.4 g, Example 33), 3-cyano-4-flurobromobenzene (0.399 g), ethanol (10 ml), 2M aqueous sodium carbonate (1.66 ml) and tetrakis(triphenylphosphine)palladium (0) (0.3 g) with heating at 80° C. for 3 hours. After work-up, the residue was purified by normal-phase HPLC eluting a gradient of 0-10% ethanol in dichloromethane to give the title compound as a solid. (0.24 g).

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US06300352B1uspto-grants-2001_10