4-CHLORO-2,5-DIFLUOROBENZALDEHYDE

Step 1: Preparation of (S, E)-N-(4-chloro-2, 5-difluorobenzylidene)-2-methylpropane-2-sulfinamide (S)-(-)-2-methyl-2-propanesulfinamide (18.88 g, 156 mmol and copper(II) sulfate (9.42 g, 212 mmol) were suspended in 1, 2-dichloroethane (283 mL at rt. 4-Chloro-2, 5-difluorobenzaldehyde (25.00 g, 142 mmol) was added and the reaction was heated to 55 C. for 12 h. The turbid yellow solution was filtered through celite and silica. The filter cake was washed with 1, 2-dichloroethane (250 mL) and then the filtrate was concentrated to give a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 8.61 (s, 1H), 8.02-7.91 (m, 2H), 1.20 (s, 9H). LCMS (POS.) m/z: 280.0 (M+H)+.General procedure: A mixture of aldehyde (1 eq.), hydroxylamine hydrochloride (1.3-2 eq.) and triethylamine (2 eq.) in dichloromethane (1.2-2.5 mL/mmol aldehyde) was stirred at room temperature for 16 hours. On completion, the reaction mixture was diluted with water and extracted with dichloromethane (3 chi 20 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the oxime intermediate. This intermediate was either purified by silica gel chromatography or used without further purification in the next step.To a solution of aldehyde in ethanol/water (8/1, v/v) at room temperature was added hydroxylamine hydrochloride (2 eq.) and sodium acetate (3 eq.). The reaction was stirred for 1-2 hour until TLC showed the reaction was complete. The mixture was concentrated in vacuo, and the residue was triturated from water, collected by filtration, washed with water and dried in vacuo to afford the oxime product, which was used as such in the next step. [00191] To a solution of oxime in N, N-dimethylformamide at room temperature was added N- chlorosuccinimide (1 eq.). The reaction was stirred for 1 or more hours until TLC showed the reaction was complete. The solution was diluted with ethyl acetate and water and filtered through Celite to remove particles. The layers were separated, and the organic layer was washed with water and brine (2x), dried with sodium sulfate, filtered, and concentrated in vacuo to afford the N- hydroxybenzimidoyl chloride product, which was used as such in the next step; Following general procedure A2, compound A-103 was prepared from

Molecular Weight:176.55
XLogP3:2.2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:175.9840487
Monoisotopic Mass:175.9840487
Topological Polar Surface Area:17.1
Heavy Atom Count:11
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes