Formaldehyde → 3-{N-[2-(chroman-3-yl)ethyl]-N-methylamino}-propionic acid methyl ester

HRID 1590549Notes

Reaction equation

HRID 1590549 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:20])[CH2:5][CH2:6][NH:7][CH2:8][CH2:9][CH:10]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[O:12][CH2:11]1.C=O.[C:23](=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>C(#N)C.O.C(O)(=O)C>[CH3:2][O:3][C:4](=[O:20])[CH2:5][CH2:6][N:7]([CH2:8][CH2:9][CH:10]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[O:12][CH2:11]1)[CH3:23]

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 14838449N-[2-(chroman-3-yl)ethyl]-N-(2-methoxycarbonylethyl)-amine hydrochloride

Product 1

HCID 545690323-{N-[2-(chroman-3-yl)ethyl]-N-methylamino}-propionic acid methyl ester

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

3.0 g (0.01 mol) of 3-{N-[2-(chroman-3-yl)ethyl]amino}propionic acid methyl ester hydrochloride are suspended with stirring in 30 ml of acetonitrile, and 4.0 ml (0.05 mol) of 37% formaldehyde in water are added thereto. 0.84 g (0.01 mol) of sodium hydrogen carbonate is then added and stirring is continued, yielding a clear solution. 1.0 g of sodium cyanoborohydride is added in portions to the solution and the pH of the suspension is then adjusted to 7 by the dropwise addition of glacial acetic acid. The reaction mixture is then stirred for 1 hour at room temperature, the solvent is distilled off under reduced pressure and the oily residue is partitioned between 50 ml of diethyl ether and 15 ml of N sodium hydrogen carbonate solution. The organic phase is separated off, dried over sodium sulfate and concentrated by evaporation. Purification by chromatography on a silica gel column (diameter 2 cm, length 30 cm, Kieselgel® Merck 60) with toluene/ethanol (9:1 parts by volume) yields 3-{N-[2-(chroman-3-yl)ethyl]-N-methylamino}-propionic acid methyl ester in the form of an oil. 3-{N-[2-(chroman-3-yl)ethyl]-N-methylamino}-propionic acid hydrochloride having a melting point of 169°-170° is obtained from the latter in a manner analogous to that described in Example 1 by heating with 20 ml of 4N hydrochloric acid.

Workup

  1. customyielding a clear solution
  2. stirringThe reaction mixture is then stirred for 1 hour at room temperature
  3. distillationthe solvent is distilled off under reduced pressure
  4. customthe oily residue is partitioned between 50 ml of diethyl ether and 15 ml of N sodium hydrogen carbonate solution
  5. customThe organic phase is separated off
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated by evaporation
  8. customPurification by chromatography on a silica gel column (diameter 2 cm, length 30 cm, Kieselgel® Merck 60) with toluene/ethanol (9:1 parts by volume)

Sources & evidence

ORD record
ord-6c1ba6e1f7f5463ba1af8e45683bc013
Source dataset
uspto-grants-1993_04
Patent number
US05204334

Reaction notes

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