Hydrochloric Acid → Indecainide

HRID 1153874Notes

Reaction equation

HRID 1153874 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 52195IndecainideYield 70%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

The pH of a cold (10° C.) solution of 12.0 ml of isopropylamine in 500 ml of acetonitrile was adjusted to 8.0 by addition of gaseous hydrogen chloride. While the reaction mixture was stirred there were added sequentially 2.0 g of sodium cyanoborohydride and 5.4 g of 6'-hydroxyspiro(9H-fluorene-9,3'-piperidine)-2'-one (the cyclic carbinol and its tautomer prepared as described in Examples 1 and 2). The reaction mixture was heated at reflux for six hours, cooled to 25° C. and then diluted by addition of 100 ml of 1N hydrochloric acid. The organic solvent was removed by evaporation under reduced pressure. The aqueous solution was washed several times with dichloromethane, made alkaline by addition of ammonium hydroxide, and the product was extracted into fresh dichloromethane. The organic extracts were combined, washed with water, dried and concentrated to dryness to give 70% yield of 9-carbamoyl-9-(3-isopropylaminopropyl)fluorene, the identity of which was confirmed by thin layer chromatographic comparison with an authenic sample (silica gel, ethyl acetate:methanol, 80:20 v/v).

Workup

  1. customprepared
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for six hours
  4. customThe organic solvent was removed by evaporation under reduced pressure
  5. washThe aqueous solution was washed several times with dichloromethane
  6. additionby addition of ammonium hydroxide
  7. extractionthe product was extracted into fresh dichloromethane
  8. washwashed with water
  9. customdried
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-54e25a79285c4941a4a098389103d94d
Source dataset
uspto-grants-1984_12
Patent number
US04486592

Reaction notes

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