Water → 1-(3-Chloro-4-methoxyphenyl)cyclopropane-1-carboxylic acid

HRID 1773955Notes

Reaction equation

HRID 1773955 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:10][C:11]#N)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].Br[CH2:14][CH2:15]Cl.[OH-:17].[Na+].[OH2:19]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:11]([OH:19])=[O:17])[CH2:15][CH2:14]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

6

Reactant 4

HCID 962Water2×HCID 78491-Bromo-2-Chloroethane2×HCID 14798Sodium Hydroxide2×HCID 15020012-(3-Chloro-4-methoxyphenyl)acetonitrile

Product 1

HCID 591294641-(3-Chloro-4-methoxyphenyl)cyclopropane-1-carboxylic acid

Reagents, catalysts & solvents 1

HCID 66133Benzyl triethylammonium chlorideCatalyst2×

Conditions

Temperature
70 °C

Procedure

A mixture of (3-chloro-4-methoxy-phenyl)-acetonitrile (320 mg, 1.76 mmol, 1.00 eq.), 1-bromo-2-chloro ethane (0.51 mL, 6.05 mmol, 3.40 eq.) and benzyltriethylammonium chloride (10 mg, 0.04 mmol, 0.02 eq.) was heated at 70° C. 50% aq. NaOH soln (1.5 mL) was slowly added and the reaction mixture was stirred at 70° C. for 18 hours. 1-Bromo-2-chloro ethane (0.26 mL, 3.03 mmol, 1.72 eq.) and a spatula tip of benzyltriethylammonium chloride were added again and the mixture was stirred at 70° C. for 3 hours. 50% aq. NaOH soln. (1.5 mL) and water (5 mL) were added and the mixture was then heated up to 130° C. and stirred at that temperature for 18 hours. The reaction mixture was allowed to cool to r.t., diluted with water (20 mL) and extracted once with AcOEt (20 mL) and once with DCM (20 mL). The basic aq. layer was acidified with conc. HCl (pH<1). The resulting precipitate was filtered and washed with 1M aq. HCl soln. The filter cake was then redissolved in DCM (20 mL) and washed with 1M HCl soln (2×20 mL) and sat. aq. NaCl soln (1×20 mL). The org. layer was dried over MgSO4, filtered, and concentrated in vacuo to give 1-(3-chloro-4-methoxy-phenyl)-cyclopropanecarboxylic acid as a yellow solid. The product was used without further purification.

Workup

  1. stirringthe mixture was stirred at 70° C. for 3 hours
  2. temperaturethe mixture was then heated up to 130° C.
  3. stirringstirred at that temperature for 18 hours
  4. temperatureto cool to r.t.
  5. extractionextracted once with AcOEt (20 mL) and once with DCM (20 mL)
  6. filtrationThe resulting precipitate was filtered
  7. washwashed with 1M aq. HCl soln
  8. dissolutionThe filter cake was then redissolved in DCM (20 mL)
  9. washwashed with 1M HCl soln (2×20 mL) and sat. aq. NaCl soln (1×20 mL)
  10. dry with materiallayer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e206e16c9fcf4d2c9573f9d1a0232eac
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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