2-Phenylethyl Acetate → 4-(5-Bromo-2-chlorobenzoyl)phenethyl acetate

To a solution of commercially available 5-bromo-2-chlorobenzoic acid (5 g, 21.23 mmol) in 30 mL of anhydrous DCM was added a catalytic amount of DMF followed by oxalyl chloride (1.95 mL, 22.3 mmol) and stirred for 2 h at room temperature. A mixture of aluminum trichloride (3.68 g, 27.6 mmol) and phenethyl acetate (3.38 mL, 21.23 mmol) in 15 mL DCM was cooled in an ice-bath and the acid chloride was transferred to it using a canula. The mixture was stirred at room temperature for 4 h. The mixture was poured into 100 mL of ice-cold water and the organic layer was isolated. The aqueous solution was extracted with 25 mL DCM. The combined organic solution was washed with brine (25 mL) and dried (Na2SO4), filtered and evaporated. Purification on silica gel using an ISCO column with 5:1 hexane:EtOAc followed by 10:1 hexane:EtOAc gave intermediate BF (2.1 g, yield 26%). 1H NMR (300 MHz, CDCl3): δ 8.12 (d, J=2.4 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.59 (d, J=2.7 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.36 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 4.31 (t, J=6.9, 6.6 Hz, 2H), 3.01 (t, J=6.9, 6.6 Hz, 2H), 2.04 (s, 3H).

1. temperaturewas cooled in an ice-bath
2. stirringThe mixture was stirred at room temperature for 4 h
3. customthe organic layer was isolated
4. extractionThe aqueous solution was extracted with 25 mL DCM
5. washThe combined organic solution was washed with brine (25 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated
9. customPurification on silica gel using an ISCO column with 5:1 hexane
10. customEtOAc gave intermediate BF (2.1 g, yield 26%)

ORD record

ord-70d5dd28a09f4ea4afae12bc11d2929b

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802637B2