Hydrochloric Acid → rac-(1R,2R)-2-(methoxycarbonyl)cyclopropane-1-carboxylic acid

HRID 456510Notes

Reaction equation

HRID 456510 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:7][C@H:6]1[C:8]([O:10]C)=[O:9])=[O:4].Cl>P([O-])([O-])([O-])=O>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:7][C@H:6]1[C:8]([OH:10])=[O:9])=[O:4]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 6429599Dimethyl trans-1,2-cyclopropanedicarboxylate

Product 1

HCID 12510972rac-(1R,2R)-2-(methoxycarbonyl)cyclopropane-1-carboxylic acidYield 93.2%

Reagents, catalysts & solvents 1

HCID 1061PhosphateSolvent

Procedure

Suspend trans-cyclopropane-1,2-dicarboxylic acid dimethylester (59.8 g, 0.378 mol) is suspended in 1.0N phosphate buffer (1.5 L, pH=7) add pig liver esterase (2.25 mL, 7500 units), and monitor NaOH consumption with a pH meter to control the reaction. After 3 h the consumption of 189 mL of 2N NaOH indicates the complete hydrolysis of the diester to the monomethylester. Acidified the clear solution by the addition of 5N HCl to a pH=1. Separate the enzyme by addition of dichloromethane (500 mL) and diatomaceous earth (25 g). Stir for 5 min, and then filter the mixture. Saturate the filtrate with NaCl, and extract with ethyl acetate (5 times). Combine the extracts, dry (Na2SO4) and evaporate to obtain 50.8 g (93%) of solid, mp 46–47° C., m/z=145 (M+H)+

Workup

  1. additionadd pig liver esterase (2.25 mL, 7500 units)
  2. customNaOH consumption with a pH meter
  3. customthe reaction
  4. customAfter 3 h the consumption of 189 mL of 2N NaOH
  5. customthe complete hydrolysis of the diester to the monomethylester
  6. customSeparate the enzyme
  7. additionby addition of dichloromethane (500 mL) and diatomaceous earth (25 g)
  8. filtrationfilter the mixture
  9. concentrationSaturate the filtrate with NaCl
  10. extractionextract with ethyl acetate (5 times)
  11. dry with materialCombine the extracts, dry (Na2SO4)
  12. customevaporate

Sources & evidence

ORD record
ord-f74e172e07464797a2cdcedefb7d07cf
Source dataset
uspto-grants-2007_03
Patent number
US07186724B2

Reaction notes

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