Реакция #1899003

Уравнение реакции

triisopropyl borate

n-butyllithium

Diisopropylamine

5-(1,3-dioxolan-2-yl)-2-fluoropyridine

→

5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-ylboronic acid

Выход 67.2%

Растворители

THF

THF

THF

Условия реакции

Обработка

1. 1
   Температураcooled in an ice water bath
2. 2
   Промывкаrinse
3. 3
   Температураto warm up to room temperature
4. 4
   workup.WAITAfter 4.5 hours
5. 5
   Другоеthe reaction was quenched with 1 N NaOH (75 mL)
6. 6
   ДругоеThe layers were separated
7. 7
   workup.ADDITIONthe aqueous phase was treated with 5 N HCl
8. 8
   ЭкстракцияThe aqueous phase was extracted with 10:1 DCM/MeOH
9. 9
   workup.ADDITION5 N HCl was added to the aqueous phase
10. 10
    Экстракцияto about 5, and extraction
11. 11
    Концентрированиеconcentrated
12. 12
    Другоеdried under high vacuum

Методика

Diisopropylamine (4.60 mL, 32.5 mmol) was dissolved in THF (80 mL) and cooled in an ice water bath. Then, n-butyllithium solution (1.6 M in hexanes, 21.0 mL, 33.6 mmol) was added via syringe. After 30 minutes, the reaction was cooled to −78° C. and 5-(1,3-dioxolan-2-yl)-2-fluoropyridine (3.73 g, 22.1 mmol) was added as a solution in THF (12 mL) dropwise over 5 minutes via syringe, followed by a THF (4 mL) rinse. The reaction was stirred at −78° C. under nitrogen for 1 hour, and then triisopropyl borate (Fluka 98+%, 8.0 mL, 34.9 mmol) was added via syringe, and the reaction was allowed to warm up to room temperature. After 4.5 hours, the reaction was quenched with 1 N NaOH (75 mL). The layers were separated, and the aqueous phase was treated with 5 N HCl to lower the pH to between 6 and 7. The aqueous phase was extracted with 10:1 DCM/MeOH. 5 N HCl was added to the aqueous phase to lower the pH to about 5, and extraction was continued with 10:1 DCM/MeOH. The organic extracts were combined, concentrated and dried under high vacuum to give 5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-ylboronic acid (3.165 g, 91% purity, 61% yield over 2 steps). MS (ESI pos. ion) m/z 214 (M+H)+.

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