4-Toluenesulfonyl chloride → HCID 131718789, compound

HRID 1492429Notes

Reaction equation

HRID 1492429 reaction equation
O[CH2:2][C@H:3]1[C@@H:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=2)[CH2:8][C@H:7]2[N:18]([CH3:19])[C@@H:4]1[CH2:5][CH2:6]2.[CH2:20]([N:22](CC)CC)C.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[C-]#N.[Na+]>C(Cl)Cl.C(OCC)C.O>[ClH:16].[Cl:17][C:12]1[CH:11]=[C:10]([C@H:9]2[CH2:8][C@H:7]3[N:18]([CH3:19])[C@:4]([C:20]#[N:22])([CH2:5][CH2:6]3)[C@@H:3]2[CH3:2])[CH:15]=[CH:14][C:13]=1[Cl:16]

Participants

8

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 8929Sodium CyanideHCID 70060541HCID 70060541, compound

Product 1

HCID 131718789HCID 131718789, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (1R,2S,3S)-2-hydroxymethyl-3-(3,4-dichloro-phenyl)tropane (6.9 g, 23 mmol), triethyl amine (7 ml, 51 mmol) and p-toluenesulphonyl chloride (6.4 g, 34 mmol) in 50 ml methylene chloride was stirred over night at room temperature followed by concentration of the reaction mixture in vacuo. Water (50 ml) and diethylether (50 ml) was added and the mixture was stirred at room temperature for 30 minutes. The ether phase was first washed once with 15 ml 1M sodium hydroxide solution followed by three times water and was finally concentrated in vacuo. The residue was dissolved in ethanol (200 ml) and sodium cyanide (2.5 g, 51 mmol) was added. The mixture was stirred at reflux temperature for two days followed by concentration in vacuo. The residue was stirred with diethyl ether and water and the ether phase was washed twice with water and concentrated in vacuo. The crude product was subjected to column chromatography using methylene chloride+acetone+methanol (4+ 1+1) as eluent and the fractions containing the product was concentrated in vacuo. The product was dissolved in a small amount of methylene chloride and a solution of hydrochloric acid in diethylether (2M) was added. The mixture was concentrated in vacuo yielding the title compound as a hydroscopic crystals.

Workup

  1. washThe ether phase was first washed once with 15 ml 1M sodium hydroxide solution
  2. concentrationwas finally concentrated in vacuo
  3. dissolutionThe residue was dissolved in ethanol (200 ml)
  4. stirringThe mixture was stirred
  5. temperatureat reflux temperature for two days
  6. concentrationfollowed by concentration in vacuo
  7. stirringThe residue was stirred with diethyl ether and water
  8. washthe ether phase was washed twice with water
  9. concentrationconcentrated in vacuo
  10. additionthe fractions containing the product
  11. concentrationwas concentrated in vacuo
  12. dissolutionThe product was dissolved in a small amount of methylene chloride
  13. additiona solution of hydrochloric acid in diethylether (2M) was added
  14. concentrationThe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-0df62d76e455493c85db93016e785998
Source dataset
uspto-grants-1994_12
Patent number
US05374636

Reaction notes

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