Реакция #51489

Уравнение реакции

sodium bicarbonate

(2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid

Lithium hydroxide monohydrate

dimethyl sulfate

→

title compound

(2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid methyl ester

Растворители

THF

Условия реакции

Обработка

1. 1
   ДругоеTo a 1-L 3-neck round bottom flask equipped with a magnetic stirrer, nitrogen inlet
2. 2
   Температураthe contents are cooled to 0°
3. 3
   ТемператураOnce cooled
4. 4
   workup.STIRRINGstirred for 30 min
5. 5
   ТемператураThe mixture is then heated to about 50°
6. 6
   ТемператураAt that time, the mixture is cooled to below 20° (solids form)
7. 7
   workup.STIRRINGstirred for 15 min
8. 8
   Экстракцияthen extracted with methyl t-butyl ether (200 mL)
9. 9
   ДругоеThe phases are separated
10. 10
    Экстракцияthe aqueous layer is extracted with methyl t-butyl ether (2×200 mL)
11. 11
    ПромывкаThe combined organic phases are washed with water (400 mL)
12. 12
    Сушкаdried over sodium sulfate
13. 13
    Фильтрацияfiltered
14. 14
    Концентрированиеconcentrated under reduced pressure
15. 15
    Другоеto give a solid
16. 16
    ДругоеThis material is then recrystallized from hexanes

Методика

To a 1-L 3-neck round bottom flask equipped with a magnetic stirrer, nitrogen inlet and thermocouple is added (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid (1,40 g, 0.133 moles, 1 equivalent) followed by THF (240 mL). Lithium hydroxide monohydrate (5.6 g, 0.133 moles, 1 equivalent) is added in a single portion and is allowed to stir for 30 min at which time, the contents are cooled to 0°. Once cooled, dimethyl sulfate (12.6 mL, 0.133 moles, 1 equivalent) is added dropwise via syringe and then stirred for 30 min. The mixture is then heated to about 50° and monitored (by HPLC) until 90% conversion had been achieved. At that time, the mixture is cooled to below 20° (solids form). The mixture is then poured into sodium bicarbonate (200 mL), stirred for 15 min then extracted with methyl t-butyl ether (200 mL). The phases are separated and the aqueous layer is extracted with methyl t-butyl ether (2×200 mL). The combined organic phases are washed with water (400 mL) dried over sodium sulfate, filtered and concentrated under reduced pressure to give a solid. This material is then recrystallized from hexanes to give the title compound, mp=81°; NMR (DMSO-d6) δ 7.51, 7.15-7.25, 4.43, 3.81, 3.00-3.26 and 1.49; CMR (DMSO-d6) δ 172.43, 163.74, 161.20, 155.67, 142.58, 112.70, 120.23, 78.69, 54.71, 52.24, 39.25 and 28.37.

Источник