Ethyl 3-bromopropionate → N-(2-Acetyl-3,4-dimethoxyphenyl)-β-alanine ethyl ester

HRID 637562Notes

Reaction equation

HRID 637562 reaction equation
[NH2:1][C:2]1[C:7]([C:8](=[O:10])[CH3:9])=[C:6]([O:11][CH3:12])[C:5]([O:13][CH3:14])=[CH:4][CH:3]=1.Br[CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].C([O-])(O)=O.[Na+]>C(N(CC)CC)C>[C:18]([CH2:17][CH2:16][NH:1][C:2]1[C:7]([C:8](=[O:10])[CH3:9])=[C:6]([O:11][CH3:12])[C:5]([O:13][CH3:14])=[CH:4][CH:3]=1)([O:20][CH2:21][CH3:22])=[O:19]

Participants

5

Reactant 3

HCID 68320Ethyl 3-bromopropionateHCID 516892Sodium BicarbonateHCID 103526301-(6-Amino-2,3-dimethoxyphenyl)ethanone

Product 1

HCID 20257123N-(2-Acetyl-3,4-dimethoxyphenyl)-β-alanine ethyl esterYield 140.1%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Triethylamine (3.80 g, 5.35 mL, 38.46 mM) was at once added under N2 to a stirred mixture of 6'-amino-2',3'-dimethoxyacetophenone (2.5 g, 12.8 mM) and ethyl 3-bromopropionate (13.93 g, 9.86 mL, 76.93 mM) at room temperature. Immediately the reaction mixture solidified. This was heated under N2 to 135°-145° C. (bath temperature) for a period of 3 hours, while periodically stirring the solid reaction mixture to form a uniformly soft, semisolid mass. After cooling, the reaction was treated with 10% NaHCO3 (50 mL) and extracted with CH2Cl2 (3×60 mL). The organic layer, after the H2O wash, drying (Na2SO4), and the removal of the solvent in vacuo, gave a dark brown oily residue (5.3 g). This was chromatographed on a column of SilicAR CC-7 (350 g, 57 cm×5 cm) packed in hexane and eluted with increasing proportions of ethyl acetate/hexane, collecting 1 L fractions. Fraction 6, eluting with 15% ethyl acetate/hexane gave, upon removal of the solvent in vacuo, purified 6'-(N-2-carbethoxyethylamino)-2',3'-dimethoxyacetophenone (0.452 g, 12%) as a light yellow oil. IR (neat) μ: 2.97, 5.75, 6.10.

Workup

  1. temperatureThis was heated under N2 to 135°-145° C. (bath temperature) for a period of 3 hours
  2. customthe solid reaction mixture
  3. customto form a uniformly soft, semisolid mass
  4. temperatureAfter cooling
  5. extractionextracted with CH2Cl2 (3×60 mL)
  6. washThe organic layer, after the H2O wash
  7. dry with materialdrying (Na2SO4)
  8. customthe removal of the solvent in vacuo

Sources & evidence

ORD record
ord-52ca856ed64d4be0bba343cec4331b9d
Source dataset
uspto-grants-1985_12
Patent number
US04556739

Reaction notes

Loading…