N1C=CN=C1.[NH2:6][C:7]([CH:9]1[CH2:13][CH:12]([F:14])[CH2:11][N:10]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=O.P(Cl)(Cl)(Cl)=O.[Cl-].[Na+]>C(OC(=O)C)C.N1C=CC=CC=1>[C:7]([C@@H:9]1[CH2:13][C@H:12]([F:14])[CH2:11][N:10]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])#[N:6]
In a 5.0 L 4-necked RB flask, fitted with a mechanical stirrer and reflux condenser, pyridine (1000 ml) and imidazole (58.6 gm, 0.86 mol) were added at 25-35° C. while stirring. The reaction mixture was cooled to 0-5° C. while stirring for 30 min, tert-butyl 2-(aminocarbonyl)-4-fluoropyrrolidine-1-carboxylate (100 gm, 0.43 mol) and phosphorous oxychloride (165.7 gm, 1.07 mol) were added slowly at 0-5° C. while stirring. After addition, the reaction mixture was maintained for 1 hr. The progress of the reaction was monitored by TLC. After ascertaining completion of the reaction by TLC, the reaction mixture was poured into an ice cold water (5 L), sodium chloride and ethylacetate (800 ml) mixture. The aqueous layer was washed with an ethyl acetate (800 ml), dilute HCl (4 100), sodium bicarbonate and saturated brine solution. The ethylacetate layer was distilled below 55° C. under vacuum and hexane (500 ml) was added to the resulting mass. Trace ethylacetate was distilled off. The resulting mass was taken as such to the next stage.
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