Hydrochloric Acid → Ethyl 2-methyl-2-(4-nitrophenyl)propanoate

HRID 2423222Notes

Reaction equation

HRID 2423222 reaction equation
[H-].[Na+].Cl[CH:4]([CH3:10])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[N+:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([O-:13])=[O:12].I[CH3:21].Cl>CN(C)C=O>[CH3:21][C:4]([C:17]1[CH:18]=[CH:19][C:14]([N+:11]([O-:13])=[O:12])=[CH:15][CH:16]=1)([CH3:10])[C:5]([O:7][CH2:8][CH3:9])=[O:6]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 7416NitrobenzeneHCID 10807Ethyl 2-chloropropionateHCID 24758Sodium hydride2×

Product 1

HCID 15544079Ethyl 2-methyl-2-(4-nitrophenyl)propanoateYield 42.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A 250 mL oven-dried flask capped with a rubber septum was evacuated and backfilled with argon. The flask was charged with NaH (7.26 g, 181 mmol, 60% dispersion in oil) anhydrous dimethylformamide (50 mL) and the flask was cooled to 0° C. Ethyl 2-chloropropionate (10.0 g, 73.2 mmol) and nitrobenzene (9.92 g, 80.5 mmol) were dissolved in anhydrous dimethylformamide (50 mL) and added dropwise to the sodium hydride slurry. The reaction was stirred for 30 min at 0° C., the cooling bath removed and the reaction was allowed to reach ambient temperature. After 1 h iodomethane (10.4 g, 73.2 mmol) was added and the mixture was stirred for an additional 30 min. The contents of the flask were poured into a mixture of ice and 1N HCl followed by three extractions with dichloromethane. The combined organic layers were washed five times with water, three times with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. Purification was performed by silica gel flash chromatography eluting with a gradient of hexanes and dichloromethane (30% hexanes in dichloromethane to 100% dichloromethane) to yield ethyl 2-methyl-2-(4-nitrophenyl)propanoate (7.32 g, 42.2%).

Workup

  1. customA 250 mL oven-dried flask
  2. customcapped with a rubber septum
  3. customwas evacuated
  4. customthe cooling bath removed
  5. customto reach ambient temperature
  6. stirringthe mixture was stirred for an additional 30 min
  7. extractionfollowed by three extractions with dichloromethane
  8. washThe combined organic layers were washed five times with water, three times with saturated aqueous sodium bicarbonate solution
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification
  13. washeluting with a gradient of hexanes and dichloromethane (30% hexanes in dichloromethane to 100% dichloromethane)

Sources & evidence

ORD record
ord-0fa68465ff2f4066968f7a0f1ff0c853
Source dataset
uspto-grants-2011_06
Patent number
US07960569B2

Reaction notes

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