Acetyl chloride → HCID 59651817, compound

Temperature

70 °C

To a solution of 3-fluoro-4-bromobenzaldehyde (20.0 g, 98.5 mmol) in dry EtOH (120 mL) was added acetyl chloride (2.04 mL, 29.6 mmol) followed by the addition of triethyl orthoformate (6.55 mL, 39.4 mmol) and the contents were heated to 70° C. for 3 h. The contents were cooled to room temperature and shifted to a rotary evaporator and subjected to reduced pressure (280 mm Hg) with bath temperature 65° C. for 45 min. The pressure was further lowered to remove all the solvent. To this mixture, fresh Ethanol (60 mL), acetyl chloride (1.5 mL), triethyl orthoformate (5.0 mL) and heated to 70° C. for 2 h. The solvent was removed under the reduced pressure and diluted with EtOAc (200 mL), washed with saturated sodium bicarbonate (3×100 mL), brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue purified by silica gel column (basified with 5% Et3N, eluent: EtOAc/hexanes, 1/20) to afford 1-bromo-4-(diethoxymethyl)-2-fluorobenzene as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.03 (t, J=8.1 Hz, 1H), 7.36-7.33 (m, 2H), 5.54 (s, 1H), 3.63-3.52 (m, 4H), 1.25 (m, 6H).

1. temperatureThe contents were cooled to room temperature
2. customshifted to a rotary evaporator
3. customsubjected to reduced pressure (280 mm Hg) with bath
4. customto remove all the solvent
5. temperatureTo this mixture, fresh Ethanol (60 mL), acetyl chloride (1.5 mL), triethyl orthoformate (5.0 mL) and heated to 70° C. for 2 h
6. customThe solvent was removed under the reduced pressure
7. additiondiluted with EtOAc (200 mL)
8. washwashed with saturated sodium bicarbonate (3×100 mL), brine
9. dry with materialdried over anhydrous sodium sulfate
10. customThe solvent was evaporated
11. customthe residue purified by silica gel column (basified with 5% Et3N, eluent: EtOAc/hexanes, 1/20)

ORD record

ord-16446995d03a408c8044c3bf34f13ccb

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080542B2