反应详情

To a solution of lithium 5-bromo-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methylcyclohexanecarbonyl)-amino]-thiophene-2-carboxylate (498 mg, 1.10 mmol) and 1,4-dioxaspiro[4,5]dec-7-en-8-boronic acid (412 mg, 1.55 mmol) in DMF (6 mL) was added 2M solution of Na2CO3 (3 mL), and the mixture was deoxygenated by bubbling nitrogen through solution for 10 min. Then Pd(PPh3)4 was added to the mixture, and it was refluxed under nitrogen for 2 h. The mixture was brought to room temperature and filtered through a celite pad washing with EtOAc and H2O. Filtrate was extracted with EtOAc (4×), then aqueous fraction was separated and acidified with 2N HCl till pH 2-3. The mixture was extracted with CH2Cl2 and CH2Cl2-MeOH, organic fraction was dried over Na2SO4 and evaporated to dryness. Crude compound was recrystallized from CH3CN to afford 453 mg (82%) of 5-(1,4-dioxa-spiro[4.5]dec-7-en-8-yl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid as a solid.

1. customthe mixture was deoxygenated
2. customby bubbling nitrogen through solution for 10 min
3. additionThen Pd(PPh3)4 was added to the mixture, and it
4. temperaturewas refluxed under nitrogen for 2 h
5. customwas brought to room temperature
6. filtrationfiltered through a celite pad
7. washwashing with EtOAc and H2O
8. extractionFiltrate was extracted with EtOAc (4×)
9. customaqueous fraction was separated
10. extractionThe mixture was extracted with CH2Cl2 and CH2Cl2-MeOH, organic fraction
11. dry with materialwas dried over Na2SO4
12. customevaporated to dryness
13. customCrude compound was recrystallized from CH3CN