Ethanol → Ethyl (3-chloro-2-fluorophenyl)acetate

A solution of 2-(3-chloro-2-fluorophenyl)acetic acid (2.56 g, 13.6 mmol) and thionyl chloride (100 mL, 1371 mmol) was stirred at 95° C. for 2 hours in a 250 mL round bottom flask. The solution was concentrated, azeotroped in toluene, and dried in vacuo to give the crude acid chloride, which was then stirred in EtOH (150 mL, 2576 mmol) at 25° C. for 16 hours. The solution was concentrated in vacuo, diluted with saturated NaHCO3 (aq) (100 mL), and extracted with EtOAc (2×100 mL). The combined organic layers were washed with saturated NaHCO3 (aq) (100 mL), with water (100 mL), and then with brine (75 mL). The organic layer was dried over MgSO4, concentrated, and purified by silica flash column chromatography (0-10% EtOAc in hexane) to give ethyl 2-(3-chloro-2-fluorophenyl)acetate (2.335 g, 79.4% yield). MS m/e=217 (M+H)+.

1. concentrationThe solution was concentrated
2. customazeotroped in toluene
3. customdried in vacuo
4. customto give the crude acid chloride, which
5. concentrationThe solution was concentrated in vacuo
6. additiondiluted with saturated NaHCO3 (aq) (100 mL)
7. extractionextracted with EtOAc (2×100 mL)
8. washThe combined organic layers were washed with saturated NaHCO3 (aq) (100 mL), with water (100 mL)
9. dry with materialThe organic layer was dried over MgSO4
10. concentrationconcentrated
11. custompurified by silica flash column chromatography (0-10% EtOAc in hexane)

ORD record

ord-049ae8ede95e4f58b8cbffca1da41f83

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07635715B2