Reaktion #51489

Reaktionsgleichung

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

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeTo a 1-L 3-neck round bottom flask equipped with a magnetic stirrer, nitrogen inlet
2. 2
   Temperaturthe contents are cooled to 0°
3. 3
   TemperaturOnce cooled
4. 4
   workup.STIRRINGstirred for 30 min
5. 5
   TemperaturThe mixture is then heated to about 50°
6. 6
   TemperaturAt that time, the mixture is cooled to below 20° (solids form)
7. 7
   workup.STIRRINGstirred for 15 min
8. 8
   Extraktionthen extracted with methyl t-butyl ether (200 mL)
9. 9
   SonstigeThe phases are separated
10. 10
    Extraktionthe aqueous layer is extracted with methyl t-butyl ether (2×200 mL)
11. 11
    WaschenThe combined organic phases are washed with water (400 mL)
12. 12
    Trocknendried over sodium sulfate
13. 13
    Filtrationfiltered
14. 14
    Einengenconcentrated under reduced pressure
15. 15
    Sonstigeto give a solid
16. 16
    SonstigeThis material is then recrystallized from hexanes

Vorschrift

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.

Quelle