Water → (S)-N-(7,8-methylenedioxy-2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine

HRID 275782Notes

Reaction equation

HRID 275782 reaction equation
[C:1](=[O:4])([O-])[O-:2].[K+].[K+].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][NH2:22])[CH2:17][CH2:16]1.[OH2:23].CN(C)[CH:26]=[O:27]>C1(C)C=CC=CC=1>[CH2:1]1[O:4][C:14]2[C:13]3[O:23][C@@H:17]([CH2:18][NH:22][CH2:21][CH:18]4[CH2:19][CH2:20][N:15]([C:10]5[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=5[O:8][CH3:7])[CH2:16][CH2:17]4)[CH2:16][O:27][C:26]=3[CH:11]=[CH:10][C:9]=2[O:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 10608971(1-(2-Methoxyphenyl)piperidin-4-yl)methanamine

Product 1

HCID 9844558(S)-N-(7,8-methylenedioxy-2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of the product from the previous reaction (0.45 g), potassium carbonate (0.32g) and 1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine (0.51 g) in dimethylformamide (4.5 ml) and toluene (10 ml) was heated at reflux temperature for 6 hours, then left to stand at room temperature for 72 hours and then heated at reflux temperature for a further 4 hours. The cooled mixture was poured into water (300 ml) and extracted with ethyl acetate (3×40 ml). The combined organic extracts were extracted with dilute aqueous hydrochloric acid (5M; 3×30 ml) and the combined aqueous extracts basified by the addition of sodium hydroxide solution (5M). The aqueous phase was extracted with ethyl acetate (3×300 ml), dried over magnesium sulphate and the solvent removed under reduced pressure to yield a yellow oil. Purification by flash column chromatography on silica eluting with a 95:5 mixture of ethyl acetate and methanol afforded (S)-N-(7,8-methylenedioxy-2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine (0.3 g) as a clear oil. Citric acid (0.14 g) in ethanol (20 ml) was added to a solution of the oil in ethanol (20 ml) and the solvent was removed under reduced pressure to afford (S)-N-(7,8-methylenedioxy-2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methyl-amine monocitrate (0.3 g) as a fawn solid; m.p 120-22° C., [α]D −35.9° (c=0.575, MeOH).

Workup

  1. additionA mixture of the product
  2. temperaturewas heated
  3. temperatureat reflux temperature for 6 hours
  4. waitleft
  5. temperatureheated
  6. temperatureat reflux temperature for a further 4 hours
  7. extractionextracted with ethyl acetate (3×40 ml)
  8. extractionThe combined organic extracts were extracted with dilute aqueous hydrochloric acid (5M; 3×30 ml)
  9. additionthe combined aqueous extracts basified by the addition of sodium hydroxide solution (5M)
  10. extractionThe aqueous phase was extracted with ethyl acetate (3×300 ml)
  11. dry with materialdried over magnesium sulphate
  12. customthe solvent removed under reduced pressure
  13. customto yield a yellow oil
  14. customPurification by flash column chromatography on silica eluting
  15. additionwith a 95:5 mixture of ethyl acetate and methanol

Sources & evidence

ORD record
ord-84e90a8ffc324ac884e9515d04f75972
Source dataset
uspto-grants-2002_03
Patent number
US06353002B2

Reaction notes

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