Sodium Iodide → ethyl [(4-methoxyphenyl)amino]acetate

HRID 1507707Notes

Reaction equation

HRID 1507707 reaction equation
[I-].[Na+].O.O.O.C([O-])(=O)C.[Na+].[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1.Br[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>O>[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:16]([NH:17][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 7732P-AnisidineHCID 7748Ethyl bromoacetateHCID 23665404Sodium Acetate Trihydrate

Product 1

HCID 6917278ethyl [(4-methoxyphenyl)amino]acetateYield 75.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of sodium iodide (122 g, 0.81 mol) and sodium acetate trihydrate (221 g, 1.62 mol) in water (200 mL) was added 4-methoxyaniline (3) (100 g, 0.81 mol) followed by ethyl 2-bromoacetate (90 mL, 812 mmol) the reaction was stirred at 90° C. for 3 h. The reaction mixture was cooled to RT and partitioned with EtOAc (1 L), the organic phase was separated, washed with water (400 mL), 1 M HCl (aq.) (3×500 mL), and the organic phase discarded. The combined acidic extracts were cooled to 0° C. and solid NaOH was added to pH 14 and the aqueous phase was extracted with EtOAc (3×400 mL). The combined organics were washed with brine (250 mL), dried (MgSO4), filtered and solvents removed in vacuo to give ethyl 2-((4-methoxyphenyl)amino)acetate (17) (128 g, 75%) as a purple oil that crystallised on standing: m/z 210 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 6.75-6.69 (m, 2H), 6.55-6.46 (m, 2H), 3.99 (t, J=6.5 Hz, 1H), 4.10 (q, J=7.1 Hz, 2H), 3.82 (d, J=6.5 Hz, 2H), 3.63 (s, 3H), 1.19 (t, J=7.1 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. custompartitioned with EtOAc (1 L)
  3. customthe organic phase was separated
  4. washwashed with water (400 mL), 1 M HCl (aq.) (3×500 mL)
  5. temperatureThe combined acidic extracts were cooled to 0° C.
  6. additionsolid NaOH was added to pH 14
  7. extractionthe aqueous phase was extracted with EtOAc (3×400 mL)
  8. washThe combined organics were washed with brine (250 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customsolvents removed in vacuo

Sources & evidence

ORD record
ord-d9b88d9f13f64cdfbf6a8dfdcd296fab
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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