Hydrochloric Acid → HCID 11817819, compound

Temperature

-78 °C

The 3-fluoro-4-(methylthio)-a-[(trimethylsilyl)-oxy]-benzeneacetonitrile (40.1 g, 149 mmol) was cooled to −78° C. in tetrahydrofuran(400 mL). Lithium hexamethydisilazide (175 mL of 1.0 M in Hexanes, 175 mmol) was added dropwise over 1 hour. The solution was stirred for 1 additional hour at −78° C. Benzylbromide (24.5 g 149 mmol) was added as a solution in tetrahydrofuran (100 mL) over 25 minutes. The solution was kept at −78° C. for 1 hour, warmed to room temperature, and kept at room temperature for six hours. The solution was poured into ethyl acetate (300 mL). Aqueous 1 N hydrochloric acid (200 mL) was added and the solution stirred for 48 hours at room temperature. The layers were separated and the organic layer collected. The organic layer was mixed with aqueous 15% sodium hydroxide and stirred for 30 minutes. The organic layer was collected washed with saturated ammounium chloride(200 mL) and solution was dried over sodium sulfate and solvent removed at reduced pressure to afford a yellow oil. The product was isolated by preparative silica chromatography followed by crystallization from 2% ethyl acetate and hexanes (400 mL). 1-[3-fluoro-4-(methylthio)phenyl]-2-phenylethanone (21.5 grams, 82.0 mmol) was obtained as white crystals. (55% yield): Mp 77.1-77.2° C. 1H NMR (CDCl3/300 MHz) 7.77, (dd, 1H, J=8.0, 1.8 Hz), 7.64 (dd, 1H, J=10.7, 1.8 Hz), 7.20-7.40 (m, 6H), 4.22 (s, 3H), 2.51 (s, 1H).

1. temperaturewarmed to room temperature
2. waitkept at room temperature for six hours
3. stirringthe solution stirred for 48 hours at room temperature
4. customThe layers were separated
5. customthe organic layer collected
6. additionThe organic layer was mixed with aqueous 15% sodium hydroxide
7. stirringstirred for 30 minutes
8. customThe organic layer was collected
9. washwashed with saturated ammounium chloride(200 mL) and solution
10. dry with materialwas dried over sodium sulfate and solvent
11. customremoved at reduced pressure
12. customto afford a yellow oil
13. customThe product was isolated by preparative silica chromatography
14. customfollowed by crystallization from 2% ethyl acetate and hexanes (400 mL)

ORD record

ord-44264a0d35ba459ca5457ca67b4d50f6

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06600052B1