1,4-Dioxane → Methyl 4-methyl-9-oxo-5,6,7,8,9,10-hexahydroacridine-1-carboxylate

HRID 521406Notes

Reaction equation

HRID 521406 reaction equation
O=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[C:8](OC)=[O:9].[NH2:12][C:13]1[CH:14]=[C:15]([CH:20]=[CH:21][C:22]=1[CH3:23])[C:16]([O:18][CH3:19])=[O:17].O1CCOCC1>O>[CH3:23][C:22]1[C:13]2[NH:12][C:2]3[CH2:7][CH2:6][CH2:5][CH2:4][C:3]=3[C:8](=[O:9])[C:14]=2[C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 170489Cyclohexanecarboxylic acid, 2-oxo-, methyl esterHCID 337778Methyl 3-amino-4-methylbenzoate

Product 1

HCID 89669513Methyl 4-methyl-9-oxo-5,6,7,8,9,10-hexahydroacridine-1-carboxylateYield 31.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of methyl 2-oxocyclohexanecarboxylate (1.0 g, 6.4 mmol), methyl 3-amino-4-methylbenzoate (1.06 g, 6.4 mmol), polyphosphoric acid (4 mL) and dioxane (6 mL) was heated at 130° C. for 2 hours. After cooling to room temperature, the mixture was diluted with water (100 mL) and the resulting precipitate was collected by filtration and dried. The solid was suspended in methanol (100 mL) and SOCl2 (10 mL) was added. The mixture was stirred at reflux for 5 hours, concentrated and treated with water (80 mL), extracted with ethyl acetate (3×80 mL). The organic layer was separated, concentrated to give the crude product. Then the mixture was purified by chromatography column on silica gel (eluted with CH2Cl2/MeOH) to afford crude product, and the final product (0.55 g) was obtained from recrystallization using MeOH as solvent. 1H NMR (DMSO-d6) δ 10.3 (s, 1H), 7.41 (d, 1H, J=7.8 Hz), 6.99 (d, 1H, J=7.8 Hz), 3.73 (s, 3H), 2.78-2.81 (m, 2H), 2.50 (s, 3H), 2.35-2.37 (m, 2H), and 1.64-1.73 (m, 4H). MS (ESI) m/e [M+1]+272.0.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe resulting precipitate was collected by filtration
  3. customdried
  4. additionSOCl2 (10 mL) was added
  5. temperatureat reflux for 5 hours
  6. concentrationconcentrated
  7. additiontreated with water (80 mL)
  8. extractionextracted with ethyl acetate (3×80 mL)
  9. customThe organic layer was separated
  10. concentrationconcentrated
  11. customto give the crude product
  12. customThen the mixture was purified by chromatography column on silica gel (eluted with CH2Cl2/MeOH)
  13. customto afford crude product

Sources & evidence

ORD record
ord-40aa67c6e29f42c98fda582dab79a74b
Source dataset
uspto-grants-2016_05
Patent number
US09328111B2

Reaction notes

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