Phenetole → (3-Bromo-4-methylphenyl)(4-ethoxyphenyl)methanone

Temperature

-5 °C

To a stirred solution of 3-bromo-4-methylbenzoic acid (1.2 g, 4.74 mmol) and oxalyl chloride (0.7 mL, 8.16 mmol) in 8 mL of CH2Cl2 was added 50 μL of DMF. The reaction mixture was stirred overnight prior to removal of the volatiles under reduced pressure using a rotary evaporator. The crude 3-bromo-4-methylbenzoyl chloride was dissolved in 10 mL of CH2Cl2 and then cooled to −5° C. prior to adding phenetole (0.63 mL, 5.0 mmol). AlCl3 (0.945 g, 7.1 mmol) was added via a solid addition funnel over 30 min. After the mixture was stirred at 5° C. for 2 h, the reaction was quenched by pouring over ice. Subsequently, the suspension was diluted with water and extracted 3× with CH2Cl2. The combined organic layers were washed 2× with 1 M HCl, once with H2O, 2× with 1 M NaOH, and 2× with brine prior to drying over Na2SO4. Recrystallization 2× from absolute EtOH provided 1.13 g of (3-bromo-4-methylphenyl)(4-ethoxyphenyl)methanone. 1H NMR (CDCl3, 300 MHz): δ 7.93 (d, J=1.6 Hz, 1H), 7.79 (d, J=8.8 Hz, 2H), 7.60 (dd, J=1.6, 8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 6.95 (d, J=8.8 Hz, 2H), 4.12 (q, J=7.0 Hz, 2H), 2.48 (s, 3H), 1.46 (t, J=7.0 Hz, 3H); MS ESI (m/z) 319 (M+1)+, calc. 318.

1. customto removal of the volatiles under reduced pressure
2. customa rotary evaporator
3. dissolutionThe crude 3-bromo-4-methylbenzoyl chloride was dissolved in 10 mL of CH2Cl2
4. stirringAfter the mixture was stirred at 5° C. for 2 h
5. customthe reaction was quenched
6. additionby pouring over ice
7. additionSubsequently, the suspension was diluted with water
8. extractionextracted 3× with CH2Cl2
9. washThe combined organic layers were washed 2× with 1 M HCl
10. dry with materialonce with H2O, 2× with 1 M NaOH, and 2× with brine prior to drying over Na2SO4
11. customRecrystallization 2× from absolute EtOH

ORD record

ord-9a4e55b5073e4493ad440e5b0d815216

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07803778B2