Hydrochloric Acid → Dimethyl (4-bromophenyl)propanedioate

HRID 251884Notes

Reaction equation

HRID 251884 reaction equation
[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][CH:6]=1.[H-].[Na+].[CH3:15][O:16][C:17](=O)[O:18]C.Cl>C1COCC1>[CH3:1][O:2][C:3](=[O:12])[CH:4]([C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][CH:6]=1)[C:17]([O:16][CH3:15])=[O:18]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 12021Dimethyl CarbonateHCID 24758Sodium hydrideHCID 316783Methyl 2-(4-bromophenyl)acetate

Product 1

HCID 21750597Dimethyl (4-bromophenyl)propanedioate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
30 °C

Procedure

At 40° C. a solution of 4-bromophenylacetic acid methyl ester (52 g) in THF (100 mL) is carefully added over a period of 40 min to a suspension of NaH (15.6 g) in dry THF (450 mL). Stirring is continued for 70 min without heating and the temperature drops to 27° C. The evolution of gas has stopped before dimethylcarbonate (76.42 mL) is added dropwise while the temperature of the mixture is maintained at 29-31° C. Stirring is continued for 22 h at rt. The mixture is cooled to −10° C. and then carefully neutralized to pH 6-7 with aq. HCl before bulk of the THF is removed in vacuo. The residue is dissolved in EA (700 mL), washed three times with 1 N aq. HCl and once with brine, dried over MgSO4. Most of the EA is evaporated before hexane is added. The product crystallizes over night at 4° C. The crystals are collected, washed with hexane and dried to give 2-(4-bromophenyl)-malonic acid dimethyl ester (45.9 g) as pale yellow crystals. 1H-NMR(D6-DMSO): 3.66 (s, 6H), 5.07 (s, 1H), 7.30-7.34 (m, 2H), 7.55-7.59 (m, 2H).

Workup

  1. temperaturewithout heating
  2. customdrops to 27° C
  3. additionis added dropwise while the temperature of the mixture
  4. stirringStirring
  5. waitis continued for 22 h at rt
  6. temperatureThe mixture is cooled to −10° C.
  7. customis removed in vacuo
  8. dissolutionThe residue is dissolved in EA (700 mL)
  9. washwashed three times with 1 N aq. HCl
  10. dry with materialonce with brine, dried over MgSO4
  11. customMost of the EA is evaporated before hexane
  12. additionis added
  13. customThe product crystallizes over night at 4° C
  14. customThe crystals are collected
  15. washwashed with hexane
  16. customdried

Sources & evidence

ORD record
ord-875f8965b84b44d6a0494bda90f4d1b3
Source dataset
uspto-grants-2011_01
Patent number
US07868012B2

Reaction notes

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