Acetic Acid → (5-Dimethylaminomethyl-2-methyl-benzofuran-3-yl)-acetic acid ethyl ester

HRID 402912Notes

Reaction equation

HRID 402912 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[C:10]2[CH:11]=[C:12]([CH:15]=O)[CH:13]=[CH:14][C:9]=2[O:8][C:7]=1[CH3:17])[CH3:2].[CH3:19][NH:20][CH3:21].C(O)(=O)C.[BH3-]C#N.[Na+]>C(O)C>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[C:10]2[CH:11]=[C:12]([CH2:15][N:20]([CH3:21])[CH3:19])[CH:13]=[CH:14][C:9]=2[O:8][C:7]=1[CH3:17])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 59192011(5-Formyl-2-methyl-benzofuran-3-yl)-acetic acid ethyl ester

Product 1

HCID 59192030(5-Dimethylaminomethyl-2-methyl-benzofuran-3-yl)-acetic acid ethyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of (5-formyl-2-methyl-benzofuran-3-yl)-acetic acid ethyl ester (1.00 g, 4.06 mmol) in anhydrous ethanol (25 mL) is added a 5 M solution of dimethylamine in ethanol (4.1 mL). The resulting reaction mixture is stirred for 18 h at room temperature. Acetic acid (1.4 mL) and NaBH3CN (279 mg, 4.22 mmol) are added and the resulting reaction mixture is heated at 50° C. for 4 h. After cooling to room temperature the solvents are removed by rotary evaporation. The residue is taken up in water, basified (pH=8) with a saturated aqueous NaHCO3 solution and extracted twice with EtOAc. The combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. The crude product is purified by flash column chromatography (silica gel, gradient of dichloromethane/methanol 10:0 to 9:1) to afford the title compound as a colorless oil (744 mg, 2.70 mmol, 67%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.39 (s, 1H), 7.31 (d, J=8.3 Hz, 1H), 7.15 (d, J=8.3 Hz, 1H), 4.14 (q, J=7.1 Hz, 2H), 3.58 (s, 2H), 3.50 (s, 2H), 2.41 (s, 3H), 2.25 (s, 6H), 1.23 (t, J=7.1 Hz, 3H). MS (ES+): 276 (M(C16H21NO3)+H)+.

Workup

  1. customThe resulting reaction mixture
  2. customthe resulting reaction mixture
  3. temperatureis heated at 50° C. for 4 h
  4. temperatureAfter cooling to room temperature the solvents
  5. customare removed by rotary evaporation
  6. extractionextracted twice with EtOAc
  7. dry with materialThe combined organic layers are dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product is purified by flash column chromatography (silica gel, gradient of dichloromethane/methanol 10:0 to 9:1)

Sources & evidence

ORD record
ord-c886091548b94ccfa4af12b4332ba801
Source dataset
uspto-grants-2014_06
Patent number
US08742132B2

Reaction notes

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