Diethyl (ethoxymethylene)malonate → HCID 13188588, compound

HRID 851085Notes

Reaction equation

HRID 851085 reaction equation
[Cl:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][CH:7]([CH3:10])[CH2:8][O:9][C:4]=2[C:3]=1[F:13].C([O:16][CH:17]=[C:18]([C:24](OCC)=O)[C:19]([O:21][CH2:22][CH3:23])=[O:20])C.O1C2C=CC=CC=2C=CN1>O>[Cl:1][C:2]1[C:3]([F:13])=[C:4]2[O:9][CH2:8][CH:7]([CH3:10])[N:6]3[CH:24]=[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:17](=[O:16])[C:11]([CH:12]=1)=[C:5]23

Participants

5

Reactant 3

HCID 6871Diethyl (ethoxymethylene)malonateHCID 13188587HCID 13188587, compoundHCID 17845026Benzoxazines

Product 1

HCID 13188588HCID 13188588, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 1.11 g (5.5 mmols) of 7-chloro-8-fluoro-3-methyl-2,3-dihydro-4H-1,4-benzoxazine and 1.4 g (6.2 mmols) of diethyl ethoxymethylenemalonate was stirred for 2 hours while heating at 130°-140° C. (bath temperature). After confirming disappearance of the starting benzoxazine compound by thin-layer chromatography, 5 g of ethyl polyphosphate was added to the reaction mixture and the mixture was again allowed to react for 1 hour at 140° C. (bath temperature). After cooling, 20 ml of water was added to the mixture and the precipitate formed was extracted with 150 ml of chloroform. The chloroform extract was dried with sodium sulfate and chloroform was then distilled off. The resulting residue was purified by silica gel (20 g) column chromatography using methanol-chloroform (5:95 by volume) as an eluant to provide 1.2 g (67.0% yield) of ethyl 9-chloro-10-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate with m.p. 263°-264° C.

Workup

  1. temperaturewhile heating at 130°-140° C. (bath temperature)
  2. additionwas added to the reaction mixture
  3. customto react for 1 hour at 140° C. (bath temperature)
  4. temperatureAfter cooling
  5. customthe precipitate formed
  6. extractionwas extracted with 150 ml of chloroform
  7. extractionThe chloroform extract
  8. dry with materialwas dried with sodium sulfate and chloroform
  9. distillationwas then distilled off
  10. customThe resulting residue was purified by silica gel (20 g) column chromatography

Sources & evidence

ORD record
ord-a77555a6d3d346c5811767907dd791fb
Source dataset
uspto-grants-1983_05
Patent number
US04382892

Reaction notes

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