Lithium Hydroxide → 3-(Methyl(phenyl)amino)-3-oxopropanoic acid

HRID 2193667Notes

Reaction equation

HRID 2193667 reaction equation
Cl[C:2](=[O:8])[CH2:3][C:4]([O:6]C)=[O:5].[CH3:9][NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Li+].[OH-]>C(Cl)Cl.O>[CH3:9][N:10]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:2](=[O:8])[CH2:3][C:4]([OH:6])=[O:5]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 7515N-MethylanilineHCID 123460Methyl malonyl chloride

Product 1

HCID 3500563-(Methyl(phenyl)amino)-3-oxopropanoic acidYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 3-chloro-3-oxopropanoate (1 mL, 9.32 mmol) and N-methyl aniline (1.01 mL, 9.32 mmol) in DCM (18.6 mL) was stirred overnight at room temperature. The solvent was removed under reduced pressure and the residue (N-methyl-N-phenyl-malonamic acid methyl ester, 2.55 g) was dissolved in THF (9 mL). A solution of LiOH×H2O (0.7 g, 18.64 mmol) in water (9 mL) was added and the mixture stirred for 1 h at room temperature. The THF was removed under reduced pressure and the remaining aqueous solution was acidified with 1N HCl (until pH˜3) then extracted with EtOAc. The organic phase was concentrated under reduced pressure to afford the acid 31 (1.67 g, 93% yield) as a brown foam. MS (m/z): 194.0 (M+H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue (N-methyl-N-phenyl-malonamic acid methyl ester, 2.55 g) was dissolved in THF (9 mL)
  3. customThe THF was removed under reduced pressure
  4. extractionthen extracted with EtOAc
  5. concentrationThe organic phase was concentrated under reduced pressure

Sources & evidence

ORD record
ord-97efcace3755422d83cd0ea97583f0e5
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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