2-Thiophenecarboxaldehyde → 2,2-Dimethoxy-N-(thiophen-2-ylmethyl)ethanamine

HRID 2267450Notes

Reaction equation

HRID 2267450 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=O.[CH3:8][O:9][CH:10]([O:13][CH3:14])[CH2:11][NH2:12].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>C(O)C>[CH3:8][O:9][CH:10]([O:13][CH3:14])[CH2:11][NH:12][CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 73642-ThiophenecarboxaldehydeHCID 89728Aminoacetaldehyde dimethyl acetalHCID 521998p-Toluenesulfonic acid monohydrateHCID 4311764Sodium borohydride

Product 1

HCID 123370202,2-Dimethoxy-N-(thiophen-2-ylmethyl)ethanamine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Thiophene-2-carboxaldehyde (22.4 g, 200 mmol) was dissolved in anhydrous ethanol (200 mL) and treated with 2,2-dimethoxyethanamine (26.6 g, 200 mmol) and para-toluenesulfonic acid hydrate (0.1 g, catalytic) and the mixture heated to reflux for 4 h. The reaction was allowed to cool down to room temperature and sodium borohydride (7.6 g, 200 mmol) was added in small portions to the reaction. Following complete addition, the reaction was stirred at room temperature for 15 min, then at reflux for 2 h. The reaction was allowed to cool down to room temperature and all the volatiles removed in vacuo. The residue was dissolved in ethyl acetate and was washed with saturated aqueous sodium bicarbonate, water and brine. The organic layer was then dried with sodium sulfate, passed through a pad of silica gel, concentrated and placed on a vacuum line to afford an off-white solid. Yield=40.1 g. MS (M+H)+ 202.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 4 h
  3. additionaddition
  4. temperatureat reflux for 2 h
  5. temperatureto cool down to room temperature
  6. customall the volatiles removed in vacuo
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. washwas washed with saturated aqueous sodium bicarbonate, water and brine
  9. dry with materialThe organic layer was then dried with sodium sulfate
  10. concentrationconcentrated
  11. customto afford an off-white solid

Sources & evidence

ORD record
ord-68c88041b32a4eda9ddf7f16b2f5a141
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

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