反応 #679546

反応方程式

tert-butyl 4-(4-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

tert-Butyl 4-(4-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

LiOH.H2O

→

title compound A5

1-(2-(2-(2-((4-(1-(tert-Butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxylic acid

溶媒

THF

MeOH

H2O

反応条件

後処理

1. 1
   その他The volatiles were removed under reduced pressure
2. 2
   workup.ADDITIONAqueous HCl (2 M, 50 mL) was added cautiously
3. 3
   その他the layers were separated
4. 4
   抽出The aqueous phase was extracted with EtOAc (2×50 mL)
5. 5
   洗浄the combined organics were washed with brine
6. 6
   乾燥dried over MgSO4
7. 7
   その他The solvent was removed in vacuo

実験手順

A solution of tert-butyl 4-(4-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A4) (0.304 g, 0.487 mmol) and LiOH.H2O (204 mg, 4.87 mmol) in THF (7 mL), MeOH (7 mL) and H2O (1.5 mL) was stirred at room temperature overnight. The resulting mixture was then heated to 40° C. and stirred for 3.5 days. The volatiles were removed under reduced pressure and the residue was taken up in EtOAc (50 mL). Aqueous HCl (2 M, 50 mL) was added cautiously and the layers were separated. The aqueous phase was extracted with EtOAc (2×50 mL), and then the combined organics were washed with brine and dried over MgSO4. The solvent was removed in vacuo to give the title compound A5 as a yellow oil (680 mg, 98%); LCMS-A: rt 6.793 min; m/z 609 [M−H]−.

出典