تفاعل #166601

معادلة التفاعل

cesium carbonate

2-chloro-4-fluoropyridine

tert-butyl carbamate

cesium carbonate

→

tert-butyl 4-fluoropyridin-2-ylcarbamate

المردود 70.1%

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThis mixture was heated
2. 2
   درجة الحرارةat reflux under nitrogen for 7 hours
3. 3
   أخرىthe reaction to completion (
4. 4
   درجة الحرارةheated a further 7 hours)
5. 5
   ترشيحfiltered through Celite
6. 6
   غسيلwashed with ethyl acetate
7. 7
   أخرىThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
8. 8
   استخلاصThe aqueous phase was extracted with ethyl acetate twice
9. 9
   غسيلThe combined organic phases were washed with brine
10. 10
    تجفيفdried with sodium sulfate
11. 11
    تركيزconcentrated under vacuum
12. 12
    أخرىpurified by column chromatography

الإجراء التجريبي

A 2 L flask was charged 2-chloro-4-fluoropyridine (20 g, 152 mmol), tert-butyl carbamate (89 g, 760 mmol), tris(dibenzylideneacetone) dipalladium (1.39 g, 1.52 mmol), X-PHOS (2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl) (1.48 g, 3.10 mmol), cesium carbonate (99 g, 588 mmol), and tetrahydrofuran (500 mL) under an atmosphere of dry nitrogen. This mixture was heated at reflux under nitrogen for 7 hours. An additional 1 equivalent of cesium carbonate was added to drive the reaction to completion (heated a further 7 hours). The mixture was cooled to ambient temperature, filtered through Celite and washed with ethyl acetate. The filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate. The aqueous phase was extracted with ethyl acetate twice. The combined organic phases were washed with brine and dried with sodium sulfate, concentrated under vacuum, and purified by column chromatography to give tert-butyl 4-fluoropyridin-2-ylcarbamate as a pale yellow solid (22.6 g).

المصدر