3-chloro-N-(3,4-difluorophenyl)propanamide → 6,7-Difluoro-3,4-dihydroquinolin-2(1h)-one

HRID 344876Notes

Reaction equation

[Cl-].[Al+3].[Cl-].[Cl-].[F:5][C:6]1[CH:7]=[C:8]([CH:15]=[CH:16][C:17]=1[F:18])[NH:9][C:10](=[O:14])[CH2:11][CH2:12]Cl>Cl>[F:18][C:17]1[CH:16]=[C:15]2[C:8](=[CH:7][C:6]=1[F:5])[NH:9][C:10](=[O:14])[CH2:11][CH2:12]2

Participants

Conditions

Temperature: 110 °C

Procedure

Aluminium chloride (134 g) is added with vigorous stirring to 3',4'-difluoro-3-chloropropionanilide (67 g) and then, after approximately 2 minutes, 3',4'-difluoro-3-chloropropionanilide (135.9 g) and aluminium chloride (272 g) are added again in small portions in the course of 15 minutes. The temperature rises spontaneously to approximately 60° C. and the reaction mixture becomes liquid. The mixture is then heated to 110° C. in the course of 20 minutes and maintained at between 110° C. and 120° C. for 2 hours. The reaction mixture (at approximately 110° C.) is poured in the course of 10 minutes with vigorous stirring into a mixture of 35% strength hydrochloric acid (840 cc) and crushed ice (1 kg). The temperature is allowed to rise to approximately 20° C. and the product is drained, washed with water (2×600 cc), ethanol (300 cc) at 5° C. and ethyl ether (2×400 cc) at approximately 20° C. 6,7-Difluoro-1,4-dihydrocarbostyril (131.58 g) is obtained in the form of a beige solid, m.p. 216° C., which is used without further treatment for the subsequent steps.

Workup

customrises spontaneously to approximately 60° C.
temperaturemaintained at between 110° C. and 120° C. for 2 hours
additionThe reaction mixture (at approximately 110° C.) is poured in the course of 10 minutes
customto rise to approximately 20° C.
washwashed with water (2×600 cc), ethanol (300 cc) at 5° C.
customat approximately 20° C

Sources & evidence

ORD record: ord-af99b5fa20a240bbb4dfd47ad1db9b35
Source dataset: uspto-grants-1991_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05053509

Reaction notes

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