تفاعل #1925208

معادلة التفاعل

4-methoxybenzyl alcohol

TsOH

4-Chloro-2-trifluoroacetylaniline, hydrochloride hydrate

NaOH

→

N-((4′-Methoxy)benzyl)-4-chloro-2-trifluoroacetylaniline

المذيبات

water toluene

toluene

water

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwere added
2. 2
   درجة الحرارةThe solution was heated
3. 3
   درجة الحرارةto reflux
4. 4
   workup.DISTILLATIONdistilled
5. 5
   غسيلwashed with saturated brine (80 kg)
6. 6
   تركيزThe organic solution was concentrated in vacuo to a volume of 35-40 L
7. 7
   workup.ADDITIONdiluted with THF (52 kg)
8. 8
   أخرىAn analytical sample was obtained
9. 9
   أخرىby removing the solvent in vacuo
10. 10
    أخرىrecrystallizing from heptane

الإجراء التجريبي

To a slurry of 4-Chloro-2-trifluoroacetylaniline, hydrochloride hydrate (40.0 kg, 144 mol) in toluene (140 kg) and water (50 L) was added 30% NaOH (18 kg) to pH 7.0. After removing the aqueous phase, 4-methoxybenzyl alcohol (20 kg, 144 mol) and TsOH (1.0 kg, 5.3 mol) were added. The solution was heated to reflux and the water/toluene azeotrope (30 L) distilled. The solution was cooled to room temperature and washed with saturated brine (80 kg). The organic solution was concentrated in vacuo to a volume of 35-40 L, then diluted with THF (52 kg). The weight percent of the title compound in toluene/THF was calculated by HPLC to be 43%. The yield based on HPLC weight % analysis was 47.7 kg (96%). An analytical sample was obtained by removing the solvent in vacuo and recrystallizing from heptane: mp 82-84° C.; 1H NMR (300 MHz, CDCl3) δ 9.04 (s,1H), 7.74 (d, J=2 Hz, 1H), 7.35 (dd, J=2, 9 Hz), 7.24 (d, J=8 Hz, 2H), 6.91 (d, J=8 Hz, 2H), 6.75 (d, J=9 Hz, 1H), 4.43 (d, J=6 Hz, 2H), 3.79 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 180.5, 159.2, 151.9, 137.4, 130.8, 128.9, 128.4, 119.9,117.0, 114.5, 114.4, 111.3, 55.3, 46.6.

المصدر