Hydrochloric Acid → HCID 18325394, compound

Temperature

-78 °C

To a stirred solution of diisopropylamine (0.295 mL, 0.0021 mol) in anhydrous tetrahydrofuran (10 mL) at room temperature under nitrogen was added in portions a 2.1 M solution of n-butyl lithium in hexanes (1.0 mL, 0.0021 mol), and the mixture cooled to −78° C. To a solution was added a solution of 4-(4′-chloro-biphenyl-4-yl)-4-oxo-butyric acid (0.288 g, 0.000997 mol) in THF (10 mL), and the mixture stirred for 1 hour. To the yellow solution was added dropwise a solution of N-fluorodibenzenesulfonamide (NFSI, 0.346 g, 0.00110 mol) in THF (10 mL), and the mixture stirred for 2 hours at −78° C. The mixture was allowed to warm to room temperature and stirred for 16 hours. The reaction was quenched with 1 M hydrochloric acid (1.1 mL, 0.0011 mol HCl), and the mixture was rotary evaporated to dryness. The residue was passed through a column of silica gel, eluting with dichloromethane-methanol (10:1 then 9:1) to give a gum. The gum was dissolved in methanol and acidified with additional 1 M hydrochloric acid (3.4 mL, 0.0034 mol HCl). The volatiles were rotary evaporated, and the resulting suspension was filtered. The filter cake was purified by chromatography on silica gel, eluting with dichloromethane-methanol (14:1) to give 0.030 g of (±)-4-(4′-chloro-biphenyl-4-yl)-3-fluoro-4-oxo-butyric acid as a white solid: mp 170-173° C.

1. stirringthe mixture stirred for 2 hours at −78° C
2. temperatureto warm to room temperature
3. stirringstirred for 16 hours
4. customthe mixture was rotary evaporated to dryness
5. washeluting with dichloromethane-methanol (10:1
6. custom9:1) to give a gum
7. filtrationthe resulting suspension was filtered
8. customThe filter cake was purified by chromatography on silica gel
9. washeluting with dichloromethane-methanol (14:1)

ORD record

ord-ac7f99b2d14c4a69aca81561cfd8aabe

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06307089B2