反応 #9708

反応方程式

NaOH

NaHCO3

N-(4-iodophenyl)-6-methyl-1,3-benzothiazol-2-amine

methyl trans-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]cyclopentanecarboxylate

dichloromethane

→

trans-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentanecarboxylic acid

収率 74.0%

溶媒

EtOH

Toluene

EtOAc

反応条件

後処理

1. 1
   その他the resulting solution was degassed
2. 2
   その他by bubbling a flow of argon for 30 minutes
3. 3
   ろ過filtered through a Celite® pad
4. 4
   その他The solvent was removed by rotary evaporation
5. 5
   濃縮The reaction mixture was concentrated under reduced pressure
6. 6
   workup.ADDITIONConcentrated HCl was added
7. 7
   抽出the suspension was extracted with EtOAc
8. 8
   洗浄The combined organic phases were washed with brine
9. 9
   乾燥dried over sodium sulfate
10. 10
    濃縮concentrated in vacuo
11. 11
    ろ過the precipitate was collected by filtration
12. 12
    洗浄washed with EtOAc, MeOH, and DCM
13. 13
    その他dried in a vacuum oven

実験手順

N-(4-iodophenyl)-6-methyl-1,3-benzothiazol-2-amine (0.28 g, 0.78 mmol) and methyl trans-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]cyclopentanecarboxylate (0.25 g, 0.71 mmol) were combined in a dry flask under argon. Toluene (15 mL), EtOH (6 mL), and saturated aqueous NaHCO3 (2 mL) were then added, and the resulting solution was degassed by bubbling a flow of argon for 30 minutes. Then [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium (II), complex with dichloromethane (1:1) (57 mg, 0.07 mmol) was added, and the resulting mixture was heated at 85° C. for 16 h. The reaction mixture was then diluted with EtOAc and filtered through a Celite® pad. The solvent was removed by rotary evaporation and the residue was brought up in MeOH. Then 1 N aqueous NaOH (2.0 mL, 2.0 mmol) was added to the suspension, and the reaction mixture was stirred at 50° C. overnight. The reaction mixture was concentrated under reduced pressure and the residue was suspended in water. Concentrated HCl was added to adjust the acidity to pH 1, and the suspension was extracted with EtOAc. The combined organic phases were washed with brine, dried over sodium sulfate, passed through a pad of silica gel, and concentrated in vacuo. The residue was brought up in EtOAc and the precipitate was collected by filtration, washed with EtOAc, MeOH, and DCM, and dried in a vacuum oven to afford trans-2-({4′-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)-cyclopentanecarboxylic acid (0.24 g, 19%). LC-MC ret. time 3.57; m/z 457.3 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 1.57–1.86 (m, 4H), 2.00 (m, 1H), 2.17 (m, 1H), 2.37 (s, 3H), 3.22 (q, 1H), 4.08 (q, 1H), 7.14 (m, 1H), 7.51 (d, 1H), 7.61 (s, 1H), 7.80 (m, 3H), 7.89 (d, 2H), 8.05 (d, 2H), 10.58 (s, 1H), 12.19 (s, 1H).

出典