تفاعل #1184101

معادلة التفاعل

Tert-butyl 6-bromo-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate

5-bromo-nicotinicacid tert-butyl ester

Na2CO3

AcOK

→

5-{1′-tert-butoxycarbonyl-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid tert-butyl ester

المذيبات

dioxane

EtOAc

H2O

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةAfter cooling down to room temperature
2. 2
   درجة الحرارةand then heated at 100° C. for 15 hours
3. 3
   غسيلwas washed with brine
4. 4
   تجفيفdried over MgSO4
5. 5
   ترشيحAfter filtration
6. 6
   أخرىthe solvents were removed in vacuo
7. 7
   أخرىthe residue was purified by silica gel column chromatography (hexane/EtOAc=10/0 to 6/4)
8. 8
   أخرىthe obtained brown solid was crystallized from EtOAc/hexane (1/1)

الإجراء التجريبي

Tert-butyl 6-bromo-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (19.8 g, 50.0 mmol), bis(pinacolato)diboran (14.0 g, 55.0 mmol), Pd(OAc)2 (560 mg, 2.50 mmol), DPPF (2.77 g, 5.00 mmol), and AcOK (5.82 g, 60.0 mmol) were suspended in dioxane (250 mL) and heated at 100° C. for 10 hours. After cooling down to room temperature, 5-bromo-nicotinicacid tert-butyl ester (14.2 g, 55.0 mmol), Pd(PPh3)4 (5.78 g, 5.00 mmol) and 2M Na2CO3 aq. (125 mL, 250 mmol) were added to the reaction mixture; and then heated at 100° C. for 15 hours. The reaction mixture was diluted with EtOAc and H2O, organic layer was washed with brine and dried over MgSO4. After filtration, the solvents were removed in vacuo and the residue was purified by silica gel column chromatography (hexane/EtOAc=10/0 to 6/4) and the obtained brown solid was crystallized from EtOAc/hexane (1/1) to afford 5-{1′-tert-butoxycarbonyl-4-oxospiro[chroman-2,4′-piperidin]-6-yl}nicotinic acid tert-butyl ester as a pale yellow solid.

المصدر