Dimethylformamide → 1-[(6-Methoxyindan-1-yl)methyl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester oxalate

HRID 2165151Notes

Reaction equation

HRID 2165151 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][CH:9]2[CH2:12]OS(C)(=O)=O)=[CH:5][CH:4]=1.[CH3:18][O:19][C:20]([C:22]1[CH2:27][NH:26][CH2:25][CH2:24][CH:23]=1)=[O:21].Br.C(N(C(C)C)CC)(C)C.CN(C)[CH:40]=[O:41]>C1(C)C=CC=CC=1>[C:40]([OH:41])(=[O:2])[C:20]([OH:19])=[O:21].[CH3:18][O:19][C:20]([C:22]1[CH2:27][N:26]([CH2:12][CH:9]2[C:10]3[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=3)[CH2:7][CH2:8]2)[CH2:25][CH2:24][CH:23]=1)=[O:21]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 15560296Guvacoline HydrobromideHCID 17883324Methanesulphonic acid (6-methoxyindan-1-ylmethyl) ester

Product 1

HCID 703582061-[(6-Methoxyindan-1-yl)methyl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester oxalate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

5.13 g (20 mmol) of methanesulphonic acid (6-methoxyindan-1-ylmethyl) ester are dissolved in 20 ml of toluene and added to a solution of 4.9 g (22 mmol) of guvacoline hydrobromide in 15 ml of dimethylformamide and 5.65 g (44 mmol) of N,N-diisopropyl-N-ethylamine. The reaction mixture is stirred at 50° under nitrogen for 24 hours. The solvents are then substantially removed under reduced pressure. The residue is dissolved in 2N hydrochloric acid, the acidic solution is extracted by shaking with diethyl ether and the ethereal phases are separated off. The acidic aqueous solution is rendered basic with saturated sodium bicarbonate solution and extracted with diethyl ether. The ethereal solutions are subsequently washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated to dryness by evaporation in vacuo. The resulting residue is purified on silica gel with dichloromethane/methanol (19:1) and the resulting eluates are concentrated to dryness by evaporation. The resulting 1-[(6-methoxyindan-1-yl)methyl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester is dissolved in diethyl ether and oxalic acid is added thereto. The oxalate which precipitates is recrystallised from isopropanol/water and from diethyl ether. 1-[(6-methoxyindan-1-yl)methyl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester oxalate of m.p. 184°-186° is obtained

Workup

  1. customThe solvents are then substantially removed under reduced pressure
  2. dissolutionThe residue is dissolved in 2N hydrochloric acid
  3. extractionthe acidic solution is extracted
  4. stirringby shaking with diethyl ether
  5. customthe ethereal phases are separated off
  6. extractionextracted with diethyl ether
  7. washThe ethereal solutions are subsequently washed with saturated sodium chloride solution
  8. dry with materialdried over magnesium sulphate
  9. concentrationconcentrated to dryness by evaporation in vacuo
  10. customThe resulting residue is purified on silica gel with dichloromethane/methanol (19:1)
  11. concentrationthe resulting eluates are concentrated to dryness by evaporation
  12. dissolutionThe resulting 1-[(6-methoxyindan-1-yl)methyl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester is dissolved in diethyl ether
  13. additionoxalic acid is added
  14. customThe oxalate which precipitates
  15. customis recrystallised from isopropanol/water and from diethyl ether

Sources & evidence

ORD record
ord-43997b83f8c846bcb6a4058fb7802b44
Source dataset
uspto-grants-1990_07
Patent number
US04939160

Reaction notes

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