Methanol → Methyl 3-(4-aminophenyl)propanoate

HRID 1966943Notes

Reaction equation

HRID 1966943 reaction equation
S(Cl)(Cl)=O.CO.[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[CH:10][CH:9]=1.[C:19]([O-])(O)=O.[Na+]>C(OCC)(=O)C>[NH2:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 754513-(4-Aminophenyl)propionic acidHCID 516892Sodium Bicarbonate2×

Product 1

HCID 417374Methyl 3-(4-aminophenyl)propanoateYield 98%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Thionyl chloride (14.6 ml, 200 mmol, 3.3 equiv) was added dropwise to a solution of dry methanol (60 ml, 1453 mmol, 24 equiv) at −10° C. After stirring for 10 minutes, 3-(4-aminophenyl)propanoic acid (10.0 g, 61 mmol) was added to give a yellow suspension. The solution stirred for 1 hour and was slowly warmed to room temperature. The resulting solution was concentrated to give a yellow solid. The solid was suspended in ethyl acetate, and NaHCO3 (aq.) was added until the salt dissolved fully. Solid sodium bicarbonate was added to give pH 8. The layers were separated and the organics were washed with brine (aq.). The resulting solution was dried over MgSO4, filtered, and concentrated to give a yellow solid (10.6 g, 98%). 1H NMR (300 MHz, CDCl3) 7.00 (d, J=8.3 Hz, 2H), 6.63 (d, J=8.3 Hz, 2H), 3.67 (s, 3H), 3.59 (bs, NH2, 2H), 2.85 (t, J=7.6 Hz, 2H), 2.58 (t, J=8.3 Hz, 2H). 13C NMR (300 MHz, CDCl3) 173.8, 144.9, 130.7, 129.3, 115.5, 51.8, 36.4, 30.4. M.S. (ESI) m/z=180.102 (M+H).

Workup

  1. customto give a yellow suspension
  2. stirringThe solution stirred for 1 hour
  3. concentrationThe resulting solution was concentrated
  4. customto give a yellow solid
  5. dissolutiondissolved fully
  6. customto give pH 8
  7. customThe layers were separated
  8. washthe organics were washed with brine (aq.)
  9. dry with materialThe resulting solution was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-a5f6f8a5dd00438fb2c28b16885d6257
Source dataset
uspto-grants-2013_04
Patent number
US08420680B2

Reaction notes

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