Hydrochloric Acid → Methyl 4-{[1-(methoxycarbonyl)cyclopropyl]oxy}-2-methyl-5-nitrobenzoate

HRID 1942544Notes

Reaction equation

HRID 1942544 reaction equation
F[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:15])[CH:3]=1.[H-].[Na+].[OH:18][C:19]1([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20]1.Cl>O1CCCC1.O>[CH3:25][O:24][C:22]([C:19]1([O:18][C:2]2[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:15])[CH:3]=2)[CH2:21][CH2:20]1)=[O:23]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 2733178Methyl 1-hydroxy-1-cyclopropane carboxylateHCID 51342041Methyl 4-fluoro-2-methyl-5-nitrobenzoate

Product 1

HCID 67330082Methyl 4-{[1-(methoxycarbonyl)cyclopropyl]oxy}-2-methyl-5-nitrobenzoateYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Methyl 4-fluoro-2-methyl-5-nitrobenzoate (43.0 g) was dissolved in tetrahydrofuran (300 ml), and thereto was added sodium hydride (55%, 9.60 g) at 0° C., and the mixture was stirred for 30 minutes. To the mixture was added dropwise a solution of methyl 1-hydroxy-1-cyclopropanecarboxylate (22.0 g) in tetrahydrofuran (300 ml) at 0° C., and the mixture was further stirred at room temperature for 3 hours. The mixture was cooled to room temperature, and water (100 ml) was added to the reaction mixture. The mixture was neutralized by addition of 1N aqueous hydrochloric acid solution, and extracted twice with ethyl acetate (300 ml). The organic layer was washed with water, a saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resultant was purified by silica gel column (hexane/ethyl acetate=3:1) to give the title compound (58.0 g).

Workup

  1. stirringthe mixture was further stirred at room temperature for 3 hours
  2. extractionextracted twice with ethyl acetate (300 ml)
  3. washThe organic layer was washed with water
  4. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous sodium chloride solution, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resultant was purified by silica gel column (hexane/ethyl acetate=3:1)

Sources & evidence

ORD record
ord-fe0421d2393b4fb4a221cb385882a8d0
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

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