Methanol → HCID 60202686, compound

HRID 1496804Notes

Reaction equation

HRID 1496804 reaction equation
C[O:2][C:3](=[O:16])[C:4]([C:9]1[CH:14]=[CH:13][C:12]([Br:15])=[CH:11][CH:10]=1)([CH:6]1[CH2:8][CH2:7]1)[CH3:5].C(OC)(=O)C1C=CC=CC=1.CO.[OH-].[K+]>O>[Br:15][C:12]1[CH:11]=[CH:10][C:9]([C:4]([CH:6]2[CH2:7][CH2:8]2)([CH3:5])[C:3]([OH:16])=[O:2])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7150Methyl BenzoateHCID 14797Potassium HydroxideHCID 68326562HCID 68326562, compound

Product 1

HCID 60202686HCID 60202686, compoundYield 115.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A 250 mL reaction vessel equipped with a condenser is charged with a mixture (9.18 g) of 2-(4-Bromo-phenyl)-2-cyclopropyl-propionic acid methyl ester (47.2 wt %, 15.3 mmoles, 1 equiv.) and methyl benzoate (19.3 wt %, 13 mmoles). The vessel is then charged with methanol (42 mL, ACS grade), water (8 mL, DI) and finally potassium hydroxide (KOH) (13.0 g, 12.7 equiv). The solution is then heated to 60±5° C. and allowed to stir for about 1.5 to 2.5 h. The colorless solution is cooled to 25±5° C. Methanol is distilled off to a minimum volume. The resulting heterogeneous mixture is acidified (pH=1) with concentrated HCl (16 mL, 37%), then extracted with methyl tert-butyl ether twice (35 mL). To the combined organic layer is added half saturated brine (40 mL). 4 N sodium hydroxide (NaOH) aqueous is added (1.6-2.3 equiv., 6-8.8 mL). The mixture is stirred for 5 min. Then the layers are separated. The organic layer is washed with brine 20 mL once and 1 N HCl 20 mL once and separated. It is concentrated to an oil to give 2-(4-Bromo-phenyl)-2-cyclopropyl-propionic acid (4.76 g). NMR assay showed 70.48 wt %; 81.4% yield.

Workup

  1. customA 250 mL reaction vessel
  2. customequipped with a condenser
  3. temperatureThe colorless solution is cooled to 25±5° C
  4. distillationMethanol is distilled off to a minimum volume
  5. extractionextracted with methyl tert-butyl ether twice (35 mL)
  6. additionTo the combined organic layer is added half saturated brine (40 mL)
  7. addition4 N sodium hydroxide (NaOH) aqueous is added (1.6-2.3 equiv., 6-8.8 mL)
  8. stirringThe mixture is stirred for 5 min
  9. customThen the layers are separated
  10. washThe organic layer is washed with brine 20 mL once
  11. custom1 N HCl 20 mL once and separated
  12. concentrationIt is concentrated to an oil

Sources & evidence

ORD record
ord-bda6edb21ecc4cfeb1746e0d3f4b3b40
Source dataset
uspto-grants-2015_12
Patent number
US09199904B2

Reaction notes

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