Water → 7-Chloro-9-chloromethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester
Reaction equation
O.[CH3:2][O:3][C:4]([C:6]1[C:7](=O)[NH:8][C:9]2[CH:10]=[C:11]3[O:21][CH2:20][CH2:19][O:18][C:12]3=[CH:13][C:14]=2[C:15]=1[CH2:16][Cl:17])=[O:5].P(Cl)(Cl)([Cl:25])=O>>[CH3:2][O:3][C:4]([C:6]1[C:7]([Cl:25])=[N:8][C:9]2[CH:10]=[C:11]3[O:21][CH2:20][CH2:19][O:18][C:12]3=[CH:13][C:14]=2[C:15]=1[CH2:16][Cl:17])=[O:5]Participants
Procedure
A 4-necked 5-L round-bottom flask is equipped with a mechanical stirrer and water-cooled condenser. Under nitrogen, the flask is charged with 9-chloromethyl-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester (Intermediate 5, 360 g, 1.16 mol), as a suspension in phosphorus oxychloride (1.8 kg). The mixture is heated to reflux generating a black solution. After being heated at reflux for 20 h, the reaction mixture is allowed to cool to ambient temperature and transferred to a 25-L separatory funnel containing 18 L of ice water. After being stirred vigorously.for 1.5 h, the precipitate is collected on a Buchner funnel, washed with water (3 L) and dried in vacuo. at 50° C. yielding 7-chloro-9-chloromethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester as a dark crystalline solid: mp 130-132° C. 1H NMR (CDCl3, 200 MHz) d 4.05 (s, 3H), 4.42 (s, 4H), 4.81 (s, 2H), 7.50 (s, 2H). Elemental analysis: Calculated for C14H11Cl2NO4: C 51.24, H 3.38, N 4.27. Found: C 51.10, H 3.34, N 4.33.
Workup
- customA 4-necked 5-L round-bottom flask is equipped with a mechanical stirrer
- temperatureThe mixture is heated
- temperatureto reflux
- temperatureAfter being heated
- temperatureat reflux for 20 h
- customtransferred to a 25-L separatory funnel
- customthe precipitate is collected on a Buchner funnel
- washwashed with water (3 L)
- customdried in vacuo
Sources & evidence
- ORD record
- ord-fcb3ef738487410398036c6a2ae46762
- Source dataset
- uspto-grants-2002_10
- Patent number
- US06462196B1
Reaction notes
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