Hydrochloric Acid → Indecainide

HRID 1153875Notes

Reaction equation

HRID 1153875 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].Cl.C([BH3-])#N.[Na+].O[CH:11]1[NH:16][C:15](=[O:17])[C:14]2([C:29]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:23]3[C:18]2=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:13][CH2:12]1>C(#N)C>[C:15]([C:14]1([CH2:13][CH2:12][CH2:11][NH:4][CH:1]([CH3:3])[CH3:2])[C:29]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)(=[O:17])[NH2:16]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6363IsopropylamineHCID 5003444Sodium cyanoborohydrideHCID 133680416'-hydroxyspiro(9H-fluorene-9,3'-piperidine)-2'-one

Product 1

HCID 52195Indecainide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
10 °C

Procedure

The general procedure thus described was repeated when a solution of isopropylamine (45.0 ml) in acetonitrile (250 ml) was cooled to 10° C. and hydrogen chloride gas introduced into the solution keeping the temperature below 15° to pH 8.5±0.3. The resultant slurry was allowed to warm to room temperature and sodium cyanoborohydride (12.0 g) added in one portion and the pH readjusted to 8.5 if necessary. 6'-Hydroxyspiro-(9H-fluorene-9,3'-piperidine)-2'-one (30.0 g) was then added and the reaction mixture heated to reflux for 2 hours. The mixture was allowed to cool to room temperaure and dilute hydrochloric acid added to pH 1-2 to destroy any excess cyanoborohydride. The acetonitrile was removed under reduced pressure and the residue basified with sodium hydroxide solution (pH 11) and extracted with dichloromethane (3×100 ml) and the combined organic layers washed with sodium hydroxide solution, dried with anhydrous sodium sulphate and evaporated to give the crystalline free amine.

Workup

  1. customthe temperature below 15°
  2. temperatureto warm to room temperature
  3. temperaturethe reaction mixture heated
  4. temperatureto reflux for 2 hours
  5. additionadded to pH 1-2
  6. customto destroy any excess cyanoborohydride
  7. customThe acetonitrile was removed under reduced pressure
  8. extractionextracted with dichloromethane (3×100 ml)
  9. washthe combined organic layers washed with sodium hydroxide solution
  10. dry with materialdried with anhydrous sodium sulphate
  11. customevaporated

Sources & evidence

ORD record
ord-cb47f211b0164d4aa8e1f16d45ed7c38
Source dataset
uspto-grants-1984_12
Patent number
US04486592

Reaction notes

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