Diazomethane → Methyl (1R,2R)-2-(3-chlorophenyl)cyclopropane-1-carboxylate

HRID 2085070Notes

Reaction equation

HRID 2085070 reaction equation
[N+](=[CH2:3])=[N-].N(N(C)[C:7](N)=[O:8])=O.[OH-:11].[K+].[Cl:13][C:14]1[CH:15]=[C:16]([CH:22]=[CH:23][CH:24]=1)[CH:17]=[CH:18][C:19](O)=O>CCOCC.O.ClCCl.CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(=O)C>[CH3:3][O:11][C:7]([C@@H:18]1[CH2:19][C@H:17]1[C:16]1[CH:22]=[CH:23][CH:24]=[C:14]([Cl:13])[CH:15]=1)=[O:8]

Participants

10

Reactant 4

HCID 9550DiazomethaneHCID 12699N-Methyl-N-nitrosoureaHCID 14797Potassium HydroxideHCID 746313-(3-Chlorophenyl)prop-2-enoic acid

Product 1

HCID 11183432Methyl (1R,2R)-2-(3-chlorophenyl)cyclopropane-1-carboxylateYield 94%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent3×HCID 21881112Ethyl ether methylene chlorideSolvent

Procedure

Diazomethane in ether was generated by adding portionwise N-nitroso-N-methyl urea to a biphasic mixture of ether (100 mL) and 2.5 M KOH in water (150 mL). The ether layer was transferred by pipette to a solution of 3-chlorocinnamic acid (1.00 g, 5.48 mmol, 1 equiv.) and palladium(II) acetate (6 mg, 0.028 mmol, 0.005 equiv.) in dichloromethane: ether (1:2, 150 mL) at 0° C. The addition was continued until a persistent yellow color remained in the solution. Stirring was continued for 2.5 h at 0° C., then approximately 3 mL acetic acid were added and the mixture was left standing at room temperature overnight. The resulting mixture was washed twice with saturated aqueous NaHCO3 solution and once with brine. It was then dried (MgSO4), filtered, and the solvent was removed in vacuo. The crude trans-2-(3-chlorophenyl)-cyclopropanecarboxylic acid methyl ester (1.09 g, 5.17 mmol, 94%) was obtained as a yellow oil.

Workup

  1. additionThe addition
  2. waitthe mixture was left
  3. waitstanding at room temperature overnight
  4. washThe resulting mixture was washed twice with saturated aqueous NaHCO3 solution and once with brine
  5. dry with materialIt was then dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-d669588c6ba14110be93b77f87096980
Source dataset
uspto-grants-2004_04
Patent number
US06720321B2

Reaction notes

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