Chemical Properties
slight yellow to white solid
Uses
4-(Chlorocarbonyl)benzoic Acid Methyl Ester, is a building block, that can be used for the synthesis of various pharmaceutical compounds. It can be used for the preparation of benzophenone residues and also for the synthesis of novel novel bulky hydrophobic retinoids.
Synthesis
This embodiment describes the synthesis of methyl 4-chlorocarbonylbenzoate. In a 4L reactor equipped with a mechanical stirrer, reflux condenser, charging funnel, thermometer, water bath and hot plate, 438 g of dimethyl terephthalate (DMT) and 2700 mL of toluene were added. The reactor was heated to about 65°C to completely dissolve the DMT. After dissolution was complete, potassium hydroxide solution (144.54 g dissolved in 700 mL of methanol) was added slowly and dropwise over 45 minutes. The reaction mixture was stirred at 65 °C for 3 h, followed by cooling to room temperature and standing overnight. The solid product was collected by filtration and washed with 3750 mL of toluene at 80 °C. After filtration again, the product was dried in an oven at 110 °C to give 465.9 g (95.3% yield).
In another 2L three-necked round-bottomed flask equipped with a mechanical stirrer, a dosing funnel, a water bath, a thermometer, nitrogen protection and a hot plate, 130.31 g of the product prepared in the previous step and 1000 mL of toluene were added. Subsequently, 48 mL of thionyl chloride was slowly added dropwise. After the dropwise addition was completed, the mixture was heated to 67°C and maintained for 3 hours. Upon completion of the reaction, it was cooled to room temperature and stirred overnight. The reaction mixture was filtered to collect the filtrate and the excess solvent was removed by distillation under reduced pressure to give 86.52 g of the target product (73% yield).
References
[1] Patent: WO2015/42561, 2015, A1. Location in patent: Paragraph 0115; 0116; 0117
[2] Patent: WO2015/42563, 2015, A1. Location in patent: Paragraph 0115; 0116; 0117
[3] Canadian Journal of Chemistry, 1974, vol. 52, p. 66 - 79
[4] Journal of Organic Chemistry, 2005, vol. 70, # 7, p. 2763 - 2770
[5] Journal of the American Chemical Society, 1957, vol. 79, p. 96
