Citric Acid → Methyl 2-(4-chloro-phenyl)-3-hydroxy-2-methyl-propionate

HRID 1357805Notes

Reaction equation

HRID 1357805 reaction equation
C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([CH3:31])[C:27](OC)=[O:28])=[CH:22][CH:21]=1.[CH2:32]=[O:33].C(O)(=O)C[C:36](CC(O)=O)(C(O)=O)[OH:37]>O1CCCC1.C(O)(=O)C>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([CH3:31])([CH2:27][OH:28])[C:32]([O:37][CH3:36])=[O:33])=[CH:24][CH:25]=1

Participants

9

Reactant 6

HCID 311Citric AcidHCID 712FormaldehydeHCID 7912DiisopropylamineHCID 8058HexaneHCID 12398854Methyl 2-(4-chlorophenyl)propanoateHCID 178418339Butyllithium

Product 1

HCID 18188180Methyl 2-(4-chloro-phenyl)-3-hydroxy-2-methyl-propionate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

35 ml of a 1.6 molar solution of n-butyllithium in hexane (61 mmol) are added dropwise to a solution of 8.1 ml of diisopropylamine (85 mmol) in 20 ml of tetrahydrofuran at −78° C. Then a solution of 10.0 g (50 mmol) of methyl 2-(4-chloro-phenyl)-propionate in 30 ml of tetrahydrofuran is added dropwise at −78° C. Gaseous formaldehyde is piped into the reaction mixture at −20° C. for 30 minutes. After the addition of 5% citric acid and glacial acetic acid the mixture is extracted with ethyl acetate. The organic phases are washed with 1N sulphuric acid, water, saturated sodium bicarbonate solution and saline solution and dried over magnesium sulphate. The crude product is purified on silica gel, eluting with cyclohexane/ethyl acetate (19:1; 9:1; 4:1; 1:1 and 0:1). The uniform fractions are combined and concentrated by evaporation.

Workup

  1. extractionis extracted with ethyl acetate
  2. washThe organic phases are washed with 1N sulphuric acid, water, saturated sodium bicarbonate solution and saline solution
  3. dry with materialdried over magnesium sulphate
  4. customThe crude product is purified on silica gel
  5. washeluting with cyclohexane/ethyl acetate (19:1; 9:1; 4:1; 1:1 and 0:1)
  6. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-0a0854b53c7a4a779e062f47eac1ac1c
Source dataset
uspto-grants-2003_07
Patent number
US06593355B2

Reaction notes

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