Hydrochloric Acid → Ethyl 2-(2,4-dimethoxybenzylamino)acetate

HRID 409323Notes

Reaction equation

HRID 409323 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH:5]=O.Cl.[CH2:14]([O:16][C:17](=[O:20])[CH2:18][NH2:19])[CH3:15].C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.[OH-].[Na+]>ClC(Cl)C>[CH2:14]([O:16][C:17](=[O:20])[CH2:18][NH:19][CH2:5][C:4]1[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:3]=1[O:2][CH3:1])[CH3:15]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 691752,4-DimethoxybenzaldehydeHCID 2723640Glycine ethyl ester, hydrochlorideHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 19895532Ethyl 2-(2,4-dimethoxybenzylamino)acetateYield 56.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of 2,4-dimethoxy-benzaldehyde (50 g, 0.30 mole), glycine ethyl ester hydrochloride (44 g, 0.32 mole) and triethylamine (43.9 mL, 0.32 mole) in dichloroethane was stirred for one hour before sodium triacetoxyborohydride (100 g, 0.47 mole) was added in four portions. The mixture was stirred for three days before it was quenched with saturated sodium bicarbonate. The organic layer was extracted with 3N HCl (2×400 mL, 2.4 mole). The aqueous layers were combined, adjusted with solid sodium hydroxide (97.68 g, 2.4 mole) to pH=8 and extracted with ethyl acetate (500 mL). The ethyl acetate extract was washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by flash column chromatography with a gradient of methanol and dichloromethane on silica gel (120 g) to give the title compound as a yellow oil (42.77 g) 1H NMR (CDCl3, 200 MHz): δ=7.11 (m, 1H), 6.41 (m, 2H), 4.15 (q, J=7.2 Hz, 2H), 3.81 (s, 3H), 3.80 (s, 3H), 3.74 (s, 2H), 3.37 (s, 2H), 1.27 (t, J=7.2 Hz, 3H).

Workup

  1. additionwas added in four portions
  2. customwas quenched with saturated sodium bicarbonate
  3. extractionextracted with ethyl acetate (500 mL)
  4. extractionThe ethyl acetate extract
  5. washwas washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography with a gradient of methanol and dichloromethane on silica gel (120 g)

Sources & evidence

ORD record
ord-8f30829b374b4f56bd447ce6d6cb406b
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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