Hydrochloric Acid → 3-(4-Methoxyphenoxy)propionic acid

HRID 1402679Notes

Reaction equation

HRID 1402679 reaction equation
[CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]([O:7][CH2:8][CH2:9]C#N)=[CH:5][CH:4]=1.Cl.O.[C:16](=[O:19])([O-])[O-:17].[Na+].[Na+]>ClCCl>[CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]([O:7][CH2:8][CH2:9][C:16]([OH:17])=[O:19])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 10340Sodium CarbonateHCID 1142473-(4-Methoxyphenoxy)propanenitrile

Product 1

HCID 2904783-(4-Methoxyphenoxy)propionic acidYield 86.04%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A 945 g (5.34 mol, 1 eq.) sample of 1 (3-(4-methoxyphenoxy)propionitrile (1)) was charged to a 22 L round bottom flask equipped with an overhead stirrer under N2. To the stirred solids, 4 L of concentrated HCl was slowly added, followed by 2 L of H2O. The reaction mixture was heated to 100° C. for 3.5 h, at which point the reaction was complete by HPLC analysis. The reaction was cooled to 10° C. by the addition of ice to the reaction mixture, and was filtered. The dried solids gave 920 g of crude 2. The crude material was dissolved in 5 L of 6 wt. % sodium carbonate (such that pH=9), and 2 L of DCM (dichloromethane) was added to the reaction vessel. After stirring thoroughly, the organic layer was separated and discarded via a separatory funnel, and the aqueous layer charged back into the 22 L flask. The pH of the aqueous layer was carefully adjusted to 4.0, by slow addition of 6 M HCl. The precipitated solids were filtered, and dried in a vacuum oven to give 900 g of 2 as a white solid (Yield: 86.04%). 1H NMR (450 MHz, CDCl3); δ=2.78 (t, 2H; CH2COOH); 3.70 (s, 3H; OCH3); 4.18 (t, 2H; OCH2); 6.78 (m, 4H; Ar—H); 13C NMR (112.5 MHz, CDCl3): δ=34.703 (CH2COOH); 55.925 (OCH3); 64.088 (OCH2); 114.855 (CH3OCCH); 115.984 (CH2OCCH); 152.723 (CH3OC); 154.302 (CH2OC); 177.386 (COOH).

Workup

  1. customequipped with an overhead stirrer under N2
  2. temperatureThe reaction was cooled to 10° C. by the addition of ice to the reaction mixture
  3. filtrationwas filtered
  4. customThe dried solids gave 920 g of crude 2
  5. additionwas added to the reaction vessel
  6. customthe organic layer was separated
  7. customdiscarded via a separatory funnel
  8. additionthe aqueous layer charged back into the 22 L flask
  9. additionThe pH of the aqueous layer was carefully adjusted to 4.0, by slow addition of 6 M HCl
  10. filtrationThe precipitated solids were filtered
  11. customdried in a vacuum oven

Sources & evidence

ORD record
ord-1f841fd1032949779010a6b389f14858
Source dataset
uspto-grants-2014_12
Patent number
US08912177B2

Reaction notes

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