Hydrochloric Acid → Methyl 2-(4-chlorophenyl)-3-hydroxypropanoate

HRID 75389

Reaction equation

HRID 75389 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[CH2:13]=[O:14].Cl>CS(C)=O.C[O-].[Na+]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH2:13][OH:14])[C:9]([O:11][CH3:12])=[O:10])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 104196Methyl 4-chlorophenylacetate

Product 1

HCID 19914733Methyl 2-(4-chlorophenyl)-3-hydroxypropanoateYield 92.2%

Reagents, catalysts & solvents 2

HCID 10942334Sodium MethoxideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Methyl 2-(4-chlorophenyl)acetate (36.7 g, 199 mmol) and paraformaldehyde (6.27 g, 209 mmol) were dissolved/suspended in DMSO (400 mL) and treated with NaOMe (537 mg, 9.94 mmol). The mixture was allowed to stir at room temperature for 2 hours, at which time the reaction was complete as determined by TLC analysis of the crude. The reaction was poured into ice-cold water (700 mL; emulsion) and neutralized with the addition of 1M HCl solution. The aqueous layer was extracted with ethyl acetate (3×), and the organics were combined. The organic layer was washed with water (2×), brine (1×), separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the crude product as an oil. The residue was loaded onto a large fitted filtered with silica gel and eluted with 9:1 hexanes:ethyl acetate and then with 1:1 hexane:ethyl acetate to give Methyl 2-(4-chlorophenyl)-3-hydroxypropanoate as an oil (39.4 g, 92%).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  2. washThe organic layer was washed with water (2×), brine (1×)
  3. customseparated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford the crude product as an oil
  8. customa large fitted
  9. filtrationfiltered with silica gel
  10. washeluted with 9:1 hexanes

Sources & evidence

ORD record
ord-a8ae8d8400e04187b82dd22fa635d699
Source dataset
uspto-grants-2014_09
Patent number
US08835434B2

Linked notes

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