Реакция #61059

Уравнение реакции

2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine

N-acetyl-L-leucine

→

(S)-2-(3-ethoxy4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine-N-acetyl-L-leucine salt

Выход 90.0%

Растворители

methanol

methanol

Условия реакции

Обработка

1. 1
   ДругоеA 3 L 3-necked round bottom flask was equipped with a mechanical stirrer
2. 2
   ТемператураThe stirred slurry was heated
3. 3
   Температураto reflux for 1 hour
4. 4
   ФильтрацияThe slurry was filtered
5. 5
   Промывкаwashed with methanol (250 mL)
6. 6
   ДругоеThe solid was air-dried
7. 7
   Другоеdried in vacuo at ambient temperature to a constant weight
8. 8
   Другоеgiving 109.5 g (98% yield) of the crude product (85.8% ee)
9. 9
   Температураto reflux for 1 hour
10. 10
    Температураcooled to room temperature
11. 11
    workup.STIRRINGstirred for an additional 3 hours at ambient temperature
12. 12
    ФильтрацияThe slurry was filtered
13. 13
    Промывкаthe filter cake was washed with methanol (200 mL)
14. 14
    ДругоеThe solid was air-dried
15. 15
    Другоеdried in vacuo at 30° C. to a constant weight

Методика

A 3 L 3-necked round bottom flask was equipped with a mechanical stirrer, thermometer, and condenser and charged with 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine (137.0 g, 500 mmol), N-acetyl-L-leucine (52 g, 300 mmol), and methanol (1.0 L). The stirred slurry was heated to reflux for 1 hour. The stirred mixture was allowed to cool to ambient temperature and stirring was continued for another 3 hours at ambient temperature. The slurry was filtered and washed with methanol (250 mL). The solid was air-dried and then dried in vacuo at ambient temperature to a constant weight, giving 109.5 g (98% yield) of the crude product (85.8% ee). The crude solid (55.0 g) and methanol (440 mL) were brought to reflux for 1 hour, cooled to room temperature and stirred for an additional 3 hours at ambient temperature. The slurry was filtered and the filter cake was washed with methanol (200 mL). The solid was air-dried and then dried in vacuo at 30° C. to a constant weight, yielding 49.6 g (90% recovery) of (S)-2-(3-ethoxy4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine-N-acetyl-L-leucine salt (98.4% ee). Chiral HPLC (1/99 EtOH/20 mM KH2PO4 @pH 7.0, Ultron Chiral ES-OVS from Agilent Technologies, 150 mm×4.6 mm, 0.5 mL/min., @240 nm): 18.4 min (S-isomer, 99.2%), 25.5 min (R-isomer, 0.8%).

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