4-chloro-2,5-difluorobenzamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyano-3,3-bis-methylsulfanyl-acrylic acid tert-butyl ester (2.94 g, 12 mmol) and 4-chloro-2,5-difluorobenzamide (2.29 g, 12 mmol) were combined in 50 mL DMF and 60% sodium hydride (1.0 g, 25 mmol) was added in a single portion. After 1 hour, the reaction mixture was added to water and the neutralized with 2N HCl. The product was extracted with ether, dried, filtered and concentrated. The product was triturated with 30% diethyl ether/hexane to give 1.85 g of a white solid that was then heated in methanol overnight. The solid that formed when the reaction mixture cooled was filtered, rinsed with a small amount of cold methanol, and dried to give the title compound as a yellow solid (1.45 g, 31% yield for the two steps): 1H NMR (DMSO-d6): δ 13 (br s, 1H), 7.8-8.0 (m, 2H), 2.4 (s, 3H), 1.5 (s, 9H). The product was extracted with ether dried filtered concentrated The product was triturated with 30% diethyl ether/hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyano-3,3-bis-methylsulfanyl-acrylic acid tert-butyl ester (2.94 g, 12 mmol) and 4-chloro-2,5-difluorobenzamide (2.29 g, 12 mmol) were combined in 50 mL DMF and 60% sodium hydride (1.0 g, 25 mmol) was added in a single portion. After 1 hour, the reaction mixture was added to water and the neutralized with 2N HCl. The product was extracted with ether, dried, filtered and concentrated. The product was triturated with 30% diethyl ether/hexane to give 1.85 g of a white solid that was then heated in methanol overnight. The solid that formed when the reaction mixture cooled was filtered, rinsed with a small amount of cold methanol, and dried to give the title compound as a yellow solid (1.45 g, 31% yield for the two steps): 1H NMR (DMSO-d6): δ 13 (br s, 1H), 7.8-8.0 (m, 2H), 2.4 (s, 3H), 1.5 (s, 9H). The product was extracted with ether dried filtered concentrated The product was triturated with 30% diethyl ether/hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyano-3,3-bis-methylsulfanyl-acrylic acid tert-butyl ester (2.94 g, 12 mmol) and 4-chloro-2,5-difluorobenzamide (2.29 g, 12 mmol) were combined in 50 mL DMF and 60% sodium hydride (1.0 g, 25 mmol) was added in a single portion. After 1 hour, the reaction mixture was added to water and the neutralized with 2N HCl. The product was extracted with ether, dried, filtered and concentrated. The product was triturated with 30% diethyl ether/hexane to give 1.85 g of a white solid that was then heated in methanol overnight. The solid that formed when the reaction mixture cooled was filtered, rinsed with a small amount of cold methanol, and dried to give the title compound as a yellow solid (1.45 g, 31% yield for the two steps): 1H NMR (DMSO-d6): δ 13 (br s, 1H), 7.8-8.0 (m, 2H), 2.4 (s, 3H), 1.5 (s, 9H). The product was extracted with ether dried filtered concentrated The product was triturated with 30% diethyl ether/hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Cyano-3,3-bis-methylsulfanyl-acrylic acid tert-butyl ester (2.94 g, 12 mmol) and 4-chloro-2,5-difluorobenzamide (2.29 g, 12 mmol) were combined in 50 mL DMF and 60% sodium hydride (1.0 g, 25 mmol) was added in a single portion. After 1 hour, the reaction mixture was added to water and the neutralized with 2N HCl. The product was extracted with ether, dried, filtered and concentrated. The product was triturated with 30% diethyl ether/hexane to give 1.85 g of a white solid that was then heated in methanol overnight. The solid that formed when the reaction mixture cooled was filtered, rinsed with a small amount of cold methanol, and dried to give the title compound as a yellow solid (1.45 g, 31% yield for the two steps): 1H NMR (DMSO-d6): δ 13 (br s, 1H), 7.8-8.0 (m, 2H), 2.4 (s, 3H), 1.5 (s, 9H). The product was extracted with ether dried filtered concentrated The product was triturated with 30% diethyl ether/hexane