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

HRID 1675842Notes

Reaction equation

HRID 1675842 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 to completion by TLC analysis of the crude. The reaction was poured into ice-cold water (700 mL; white emulsion) and neutralized with the addition of 1M HCl solution. The aqueous portion was extracted with ethyl acetate (3×), and the organics were combined. The organic portion was washed with water twice, once with brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the crude product as a yellow oil. The residue was loaded onto a large fritted filtered with silica gel and eluted with 9:1 hexanes:ethyl acetate until the starting material/olefin were collected. The plug was then eluted with 1:1 hexanes:ethyl acetate until the pure desired product was eluted completely. The concentrated pure fractions yielded methyl 2-(4-chlorophenyl)-3-hydroxypropanoate as a colorless oil (39.4 g, 92%).

Workup

  1. extractionThe aqueous portion was extracted with ethyl acetate (3×)
  2. washThe organic portion was washed with water twice
  3. customonce with brine, separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford the crude product as a yellow oil
  8. washeluted with 9:1 hexanes
  9. customethyl acetate until the starting material/olefin were collected
  10. washThe plug was then eluted with 1:1 hexanes
  11. washethyl acetate until the pure desired product was eluted completely

Sources & evidence

ORD record
ord-8736170583de429b9e3c33e9527d7721
Source dataset
uspto-grants-2011_08
Patent number
US08003651B2

Reaction notes

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