Hydrochloric Acid → 2-Chloro-3-(4-hydroxymethyl-phenyl)-propionic acid methyl ester

HRID 709447Notes

Reaction equation

HRID 709447 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.[ClH:10].N([O-])=O.[Na+].[C:15]([O:19][CH3:20])(=[O:18])[CH:16]=[CH2:17]>CC(C)=O.CO.O.C([O-])(O)=O.[Na+].[Cu]I>[CH3:20][O:19][C:15](=[O:18])[CH:16]([Cl:10])[CH2:17][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 7294Methyl AcrylateHCID 693314-Aminobenzyl alcoholHCID 23668193Sodium Nitrite

Product 1

HCID 866502982-Chloro-3-(4-hydroxymethyl-phenyl)-propionic acid methyl esterYield 40.2%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 180AcetoneSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the (4-amino phenyl) methanol (18.47 g, 0.15 mol) in acetone (400 mL) and methanol (200 mL) was added conc. HCl (54.69 g, 1.5 mol) followed by the dropwise addition of an aqueous solution of NaNO2 (11.38 g, 0.165 mol) in water (50 mL) under ice bath cooling. The mixture was stirred for 1 h at 0° C. The ice bath was removed and the methyl acrylate (64.56 g, 0.75 mol) was added followed by CuI (4.28 g, 0.022 mol). After being stirred for 6 h at ambient temperature, the mixture was diluted with sat. aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were dried (MgSO4) and the solvent was subsequently evaporated under reduced. The remaining crude product was purified by chromatography. The crude product was purified by flash chromatography using DCM/MeOH 95:5 as the eluent to afford the product was obtained as an oil (13.8 g, 32%). 1H NMR (400 MHz, CDCl3): δ 7.24 (d, 2H), 7.19 (d, 2H), 4.59-4.63 (m, 2H), 4.42 (t, 1H), 3.72 (s, 3H), 3.36-3.31 (dd, 1H), 3.17-3.12 (dd, 1H), 1.87 (s, 1H).

Workup

  1. temperaturecooling
  2. customThe ice bath was removed
  3. stirringAfter being stirred for 6 h at ambient temperature
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. customthe solvent was subsequently evaporated
  7. customThe remaining crude product was purified by chromatography
  8. customThe crude product was purified by flash chromatography
  9. customto afford the product

Sources & evidence

ORD record
ord-3c7d9acca0cc4efb8ec3bd652c172a9a
Source dataset
uspto-grants-2015_11
Patent number
US09181181B2

Reaction notes

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