تفاعل #9635

معادلة التفاعل

Na2CO3

Methyl cis-2-(4-bromobenzoyl)cyclohexanecarboxylate

4-amino phenyl boronic acid

dichloromethane

→

methyl cis-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclohexanecarboxylate

المذيبات

EtOAc

EtOH

Toluene

ظروف التفاعل

المعالجة

1. 1
   أخرىresulting solution
2. 2
   أخرىwas degassed for 30 minutes
3. 3
   درجة الحرارةThe mixture was cooled to rt
4. 4
   أخرىThe solvent was removed by rotary evaporation
5. 5
   workup.ADDITIONWater and EtOAc were added
6. 6
   استخلاصthe aqueous layer was extracted with EtOAc
7. 7
   غسيلThe combined organic phases were washed with water, brine
8. 8
   تجفيفdried over anhydrous sodium sulfate
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated in vacuo
11. 11
    أخرىThe residue was purified by flash chromatography (Biotage Flash 40M)

الإجراء التجريبي

Methyl cis-2-(4-bromobenzoyl)cyclohexanecarboxylate (1.76 g, 5.41 mmol) and 4-amino phenyl boronic acid (1.13 g, 6.49 mmol) were added to a clean dry flask under argon. Toluene (50 mL), EtOH (20 mL), and 3 M aqueous Na2CO3 (14 mL, 43 mmol) were added, and resulting solution was degassed for 30 minutes by using a flow of argon. Then [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II), 1:1 complex with dichloromethane (442 mg, 0.54 mmol) was added and the resulting mixture was heated at 85° C. for 16 h. The mixture was cooled to rt, and then diluted with EtOAc and passed through a Celite® pad. The solvent was removed by rotary evaporation. Water and EtOAc were added, and the aqueous layer was extracted with EtOAc. The combined organic phases were washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (Biotage Flash 40M) using 33 to 40% ethyl acetate in hexane to afford methyl cis-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclohexanecarboxylate.(1.54 g, 84%). LC-MS ret. time 3.99; m/z 338 (MH+); 1H NMR (400 MHz, CD2Cl2) δ 1.37–1.53 (m, 3H), 1.74–1.88 (m, 2H), 1.90–1.99 (m, 1H), 2.04–2.22 (m, 2H), 2.75 (m, 1H), 3.59 (s, 3H), 3.90 (q, 1H), 6.79 (m, 2H), 7.48 (m, 2H), 7.63 (m, 2H), 7.89 (m, 2H).

المصدر