Thionyl Chloride → 7-Fluorobenzofuran

To a solution of 7-fluoro-2,3-dihydrobenzofuran-3-ol (4.6 g, 29 8 mmol) in pyridine (93 mL) at 0° C. was added SOCl2 (21.7 mL, 298 mmol) dropwise. Upon completion of addition, the mixture was stirred at 0° C. for 1.5 h. At the conclusion of this period, the reaction mixture was carefully quenched with aqueous NaHCO3 (saturated, 100 mL) to reach a pH=9. Once at the prescribed pH, the reaction mixture was extracted with CH2Cl2 (4×15 mL). The combined organic layers were washed with aqueous NaHCO3 (5%, 40 mL), water (40 mL), and then concentrated to yield the crude product. The crude product was dissolved in CH2Cl2 (50 mL), washed with aqueous HCl (1 N, 5×10 mL), and then water (40 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated to afford Compound 1C as a brown oil (2.56 g). 1H NMR (500 MHz, CDCl3) δ ppm 7.67 (d, J=2.2 Hz, 1 H), 7.33-7.40 (m, 1 H), 7.17 (td, J=8.0, 4.4 Hz, 1 H), 7.04 (dd, J=10.7, 8.0 Hz, 1 H), 6.79-6.85 (m, 1 H).

1. additionUpon completion of addition
2. customAt the conclusion of this period, the reaction mixture was carefully quenched with aqueous NaHCO3 (saturated, 100 mL)
3. extractionOnce at the prescribed pH, the reaction mixture was extracted with CH2Cl2 (4×15 mL)
4. washThe combined organic layers were washed with aqueous NaHCO3 (5%, 40 mL), water (40 mL)
5. concentrationconcentrated
6. customto yield the crude product
7. washwashed with aqueous HCl (1 N, 5×10 mL)
8. customThe organic layer was separated
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-31dd6d92038d443d9bf2aac8df840143

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729084B2