3-Chloro-4-methylbenzonitrile

white to light yellow crystal powder

In a 1 L four-necked flask, 161.4 g of dimethyl 2- (4-cyano-2-chlorophenyl) -1, 3-propanedioate (1 eq)21.7 grams of water (2 eq), 140.9 grams of 95percent anhydrous calcium chloride (2 eq) and 606 grams of N, N-dimethylacetamide were added, Stirring temperature, 140 ~ 145 incubated for 20 to 24 hours, cooled to 30 ° C, was added 352.5 g of water, 303 grams of methylene chloride, concentrated hydrochloric acid was added dropwise about 70.2 grams, the system pH = 5 ~ 7, liquid separation, the aqueous layer was extracted with dichloromethane, the organic phase combined, The organic phase was concentrated under reduced pressure to give a DMAc concentrated solution of 3-fluoro-4-methylbenzonitrile, the vacuum distillation was continued, 3-Chloro-4-methylbenzonitrile was collected until no product was distilled off to give 75.9 g of a white solid in a yield of 83.0percent.To a solution of General procedure: A 1.0 M solution of hydroxylamine hydrochloride in MeOH (2.0eq) and a 1.0 M solution of KOH in MeOH (2.0 eq) were combined at 0C and stirred for ~30 min (slowly warming from 0C to rt). The potassium chloride salt formed was removed by filtration. The filtrate was added to the nitrile 21 [1.0 eq; the corresponding nitrile was either purchased from commercial source (analogs 21a-l and 21o), or synthesized starting from a commercial nitrile, which was further modified via a Suzuki coupling reaction using established methods (21m-n)] and the mixture was heated at 60C for 17-24h. MeOH was removed under vacuum and the residue was diluted with EtOAc, washed with brine, and the organic layer was concentrated. The product 22 was typically obtained in quantitative yield and >90% purity, and was used in the next step without further purification.

Molecular Weight:151.59
XLogP3:3.3
Hydrogen Bond Acceptor Count:1
Exact Mass:151.0188769
Monoisotopic Mass:151.0188769
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes