Triethylamine → (5-Bromo-3-pyridinyl)methanol

Temperature

0 °C

5-Bromonicotinic acid (1.00 g; 4.95 mmol) is dissolved in 30 mL anhydrous THF and triethylamine (0.76 mL; 5.44 mmol) is added by syringe, the flask is flushed with argon and cooled to 0° C. Ethylchloroformate (0.52 mL; 5.44 mmol) is then added dropwise by syringe and the mixture is stirred at RT for 60 min. The crude mixture is filtered and the residue is washed twice with 5 mL THF, the filtrate is transferred to a 100 mL RBF and cooled to 0° C. Sodium borohydride (468 mg: 12.4 mmol) is added in portions, followed by 5 mL H2O which is added dropwise via a syringe. The mixture is stirred at RT overnight and then concentrated in vacuo. The crude product is extracted 6 times with EtOAc, the organic layers are combined and dried over anhydrous sodium sulfate, concentrated in vacuo and deposited on silica. Purification by column chromatography on silica gel (pre washed with 1% NEt3 in hexanes) using a solvent gradient from hexanes to EtOAc and then to 50% MeOH in EtOAc, led to the isolation of the product as a clear, colorless oil (426 mg, 46% yield).

1. customthe flask is flushed with argon
2. filtrationThe crude mixture is filtered
3. washthe residue is washed twice with 5 mL THF
4. temperaturecooled to 0° C
5. additionis added dropwise via a syringe
6. stirringThe mixture is stirred at RT overnight
7. concentrationconcentrated in vacuo
8. extractionThe crude product is extracted 6 times with EtOAc
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated in vacuo
11. customPurification by column chromatography on silica gel (pre washed with 1% NEt3 in hexanes)

ORD record

ord-3a482f194802430e96abde798a0ec601

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08816082B2