ETHYL 4-CHLOROBENZOYLFORMATE

Step 1: General procedure: alcohols0.6 mmolbenzoylacetonitrile0.4 mmolTHF2 mLwere added to grass tube. The reaction mixture was irradiated byone halogen tungsten lamp (500W) for 24 h accompanied with a fan beingsufficient to allow reaction temperature down to room temperature. After thereaction was completed (monitored by TLC), the reaction liquid was purifiedby chromatography on silica gel (20:1 petroleum ether/EtOAc) to give theproduct 3a-3s.General procedure: β-Oxo-benzenepropanenitrile 1(1.0 mmol), PIDA (2.2 mmol) were dissolved in EtOH (8 mL) and stirred under refluxing for 0.5h. After the reaction was completed (monitored by TLC), thereaction mixture was concentrated under vacuum. The residue was purified by chromatographyon silica gel (20:1 petroleum ether/EtOAc) to give the product 3a-o .Thesolvent for the synthesis of 3o was MeOH.Reference Example-1 Example 1b Reference Example-1 A solution of 1-bromo-4-chlorobenzene (15.0 g, 38.4 mmol) in THF was added dropwise to a suspension of magnesium (2.1 g, 86.2 mmol) in THF at 40 C. (oil bath temperature) in the presence of a catalytic amount of iodine in an argon gas atmosphere, whereby a Grignard reagent was prepared. The Grignard reagent was added dropwise to a solution of diethyl oxalate (17.7 g, 94.2 mmol) in THF at -45 C., and the temperature was slowly raised to room temperature, followed by stirring for 18 hours. After the reaction was completed, the reaction solution was poured into ice, then, acidified with concentrated hydrochloric acid, and the resultant product was extracted with ether (100 mL*2). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, whereby a yellow oily crude product (14.8 g) was obtained. This was purified by silica gel column chromatography (hexane:ethyl acetate=5:1), whereby Reference Production Example 8 In 140 ml of tetrahydrofuran were added 40.0 g of 4-bromochlorobenzene and 5.33 g of magnesium under nitrogen atmosphere, and stirred to prepare Grignard reagent. In 750 ml of tetrahydrofuran was dissolved 49.3 g of diethyl oxalyl, and the Grignard reagent was added dropwise at -70C over 30 minutes. The reaction mixture was warmed to room temperature over 2 hours, and stirred at room temperature for 2 hours. After addition of ice water and saturated ammonium chloride aqueous solution, the organic solvent was removed by distillation under reduce pressure from the reaction mixture. The residue was filtered, and the filtrate was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 22.1 g of

Molecular Weight:212.63
XLogP3:2.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:212.0240218
Monoisotopic Mass:212.0240218
Topological Polar Surface Area:43.4
Heavy Atom Count:14
Complexity:219
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes