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

HRID 1067476Notes

Reaction equation

HRID 1067476 reaction equation
C([Li])CCC.Cl.C(C1C=CC(NCC2N(C)C3C=CC(CN4C=C([C:34]([O:36][CH2:37]C)=[O:35])N=C4C)=CC=3N=2)=CC=1)(=N)N.C(N[CH:44]([CH3:46])[CH3:45])(C)C.[Cl:47][C:48]1[CH:53]=[CH:52][C:51](C(C)C(OC)=O)=[CH:50][CH:49]=1.C=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:65]>O1CCCC1.C(O)(=O)C>[Cl:47][C:48]1[CH:49]=[CH:50][C:51]([C:44]([CH3:45])([CH2:46][OH:65])[C:34]([O:36][CH3:37])=[O:35])=[CH:52][CH:53]=1

Participants

9

Reactant 6

HCID 311Citric AcidHCID 712FormaldehydeHCID 7912DiisopropylamineHCID 12398854Methyl 2-(4-chlorophenyl)propanoateHCID 211939592-(4-Amidinophenylaminomethyl)-1-methyl-5-[(2-methyl-4-ethoxycarbonyl-imidazol-1-yl)-methyl]-benzimidazole-hydrochlorideHCID 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 10 (61 mmol) are added dropwise to a solution of 8.1 ml of diisopropylamine (85 mmol)l in 20 ml tetrahydrofuran at −78° C. Then a solution of 10.0 g (50 mmol) of methyl 2-(4-chloro-phenyl)-propionate in 30 ml tetrahydrofuran is added dropwise at −78° C. Formaldehyde gas is then 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;

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

Sources & evidence

ORD record
ord-52cc3094cc2249a7b289f22d40f06594
Source dataset
uspto-grants-2001_06
Patent number
US06248770B1

Reaction notes

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