Tetrahydrofuran → HCID 22620184, compound

Temperature

-78 °C

To a stirred mixture of 4-chloropyridine hydrochloride (3 g, 20 mmol) in 200 mL of THF at −78° C. was added 24 mL (48 mmol) of pentylmagnesium bromide (2M soln in ether) slowly dropwise. After being stirred at −78° C. for 20 minutes, phenyl chloroformate (2.51 mL, 20 mmol) was added and the mixture was stirred for 30 minutes at −78° C. The cooling bath was removed and the reaction mixture was allowed to stir while slowly warming to room temperature. Aqueous 20% NH4Cl (50 mL) and ether (80 mL) were added, the layers were separated, and the queous phase was extracted twice with ether. The combined organic extracts were washed successively with 50 mL portions of saturated aqueous CuSO4, water, saturated NaHCO3, and brine. The organic phase was dried over MgSO4, filtered through Celite, and evaporated to give 6.4 g (quantitative) of the crude product. This crude material was used directly in the next step to make the N-Boc derivative. 1H NMR (250 MHz) δ7.52-6.99 (m, 5 H), 5.63 (d, 1 H), 5.24 (m, 1 H), 4.95 (m, 1 H), 1.93-1.16 (m, 8 H), 0.87 (t, 3 H).

1. stirringthe mixture was stirred for 30 minutes at −78° C
2. customThe cooling bath was removed
3. stirringto stir
4. temperaturewhile slowly warming to room temperature
5. additionAqueous 20% NH4Cl (50 mL) and ether (80 mL) were added
6. customthe layers were separated
7. extractionthe queous phase was extracted twice with ether
8. washThe combined organic extracts were washed successively with 50 mL portions of saturated aqueous CuSO4, water, saturated NaHCO3, and brine
9. dry with materialThe organic phase was dried over MgSO4
10. filtrationfiltered through Celite
11. customevaporated

ORD record

ord-5a87a46a2506443b840b4a16afede420

Source dataset

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06369078B1