HCID 10547933, compound → HCID 70102228, compound

HRID 964002Notes

Reaction equation

HRID 964002 reaction equation
B.CSC.[O:5]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH2:7][CH:6]1[CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([C:22]([NH:24]C2C=CC=CC=2OC)=O)[CH2:18][CH2:17]1>O1CCCC1>[O:5]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH2:7][CH:6]1[CH2:15][N:16]1[CH2:17][CH2:18][CH:19]([CH:22]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:5][CH3:6])[NH2:24])[CH2:20][CH2:21]1

Participants

4

Reactant 2

HCID 10547933HCID 10547933, compoundHCID 12423031(Dimethyl sulfide)trihydroboron

Product 1

HCID 70102228HCID 70102228, compoundYield 189.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

Borane-dimethyl sulphide complex (1M solution in dimethyl sulphide; 0.5 ml) was added dropwise under nitrogen to a solution of 1-(1,4-benzodioxan-2-ylmethyl)-N-(2-methoxyphenyl)piperidine-4-carboxamide (0.35 g) in dry tetrahydrofuran (25 ml) and then the mixture was heated under reflux for 2 hours. The reaction was cooled and the solvents removed in vacuo. The residue was diluted cautiously with dilute hydrochloric acid (1M; 70 ml) and heated at 95° C. for 1.5 hours. The aqueous mixture was cooled and basified by the addition of aqueous sodium hydroxide solution (2.5M), there the product was extracted into dichloromethane. The organic extract was washed with water, then dried over magnesium sulphate, filtered, and the solvent removed in vacuo to yield 1-[1-(1,4-benzodioxan-2-ylmethyl)piperid-4-yl]-N-(2-methoxyphenyl) methylamine (0.32 g). The procedure was repeated using 1-(1,4-benzodioxan-2-ylmethyl)-N-(2-methoxyphenyl)piperidine-4-carboxamide (1.37 g, prepared in a similar manner to that described above). The products of the two reactions were combined and dissolved in ether. Hydrogen chloride was bubbled through the solution and the resulting solid precipitate collected by filtration (1.2 g). The solid was dissolved in saturated aqueous sodium hydrogen carbonate solution (100 ml) and the resulting oil extracted into ethyl acetate (100 ml). An excess of a saturated solution of oxalic acid in ethyl acetate was added and the solid precipitate was collected by filtration and dried in vacuo at 50° C. to yield 1-[1-(1,4-benzodioxan-2-ylmethyl) piperid-4-yl]-N-(2-methoxyphenyl)methylamine mono-oxalate (0.78 g), m.p. 215°-218° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hours
  3. temperatureThe reaction was cooled
  4. customthe solvents removed in vacuo
  5. additionThe residue was diluted cautiously with dilute hydrochloric acid (1M; 70 ml)
  6. temperatureThe aqueous mixture was cooled
  7. additionbasified by the addition of aqueous sodium hydroxide solution (2.5M), there the product
  8. extractionwas extracted into dichloromethane
  9. extractionThe organic extract
  10. washwas washed with water
  11. dry with materialdried over magnesium sulphate
  12. filtrationfiltered
  13. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-2ba728ff974a4d28a49a19dd704a7990
Source dataset
uspto-grants-1998_06
Patent number
US05767116

Reaction notes

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