Réaction #74083

Équation de réaction

1-(5-bromo-2-hydroxyphenyl)ethanone

N-methylpiperazine

→

desired product

Rendement 51.0%

1-[2-hydroxy-5-(4-methylpiperazin-1-yl)phenyl]ethanone

Rendement 51.0%

Solvants

THF

Conditions de réaction

Traitement

1. 1
   AutreThe volatiles were removed in vacuo
2. 2
   workup.DISSOLUTIONthe obtained residue was dissolved with water and 1 N HCl (pH=6)
3. 3
   LavageThe organic phase was washed with brine
4. 4
   Séchagedried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   AutreThe residue was purified by flash column chromatography (DCM gradient to 10% MeOH/DCM)

Mode opératoire

1-(5-bromo-2-hydroxyphenyl)ethanone 1.0 g (4.65 mmol) in THF (10 ml), N-methylpiperazine 0.83 ml (7.45 mmol), LiHMDSA 16.2 ml (16.2 mmol), Pd2(dba)3 68 mg (0.074 mmol) and 2-dicyclohexylphosphino-2′-N,N-dimethylaminobiphenyl 29.3 mg (0.074 mmol) were combined under argon in a capped vial and stirred at 70° C. for 40 minutes. The volatiles were removed in vacuo, the obtained residue was dissolved with water and 1 N HCl (pH=6) and portioned with DCM. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (DCM gradient to 10% MeOH/DCM) to provide 532 mg (51%) of desired product as a brown solid. LC/MS (254 nm) HPLC method 2 Rt 3.34 min. 1H NMR (401 MHz, DMSO-d6) δ 11.45 (s, 1H), 7.21-7.28 (m, 2H), 6.80-6.93 (m, 1H), 2.98-3.10 (m, 4H), 2.63 (s, 3H), 2.44-2.48 (m, 4H), 2.23 (s, 3H). HRMS (ESI) calcd for C13H18N2O2 [M+H]+ 235.1441 Found 235.1448.

Source