Sodium Hydroxide → (6-Fluorochroman-3-YL)methanamine

HRID 1196061Notes

Reaction equation

HRID 1196061 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:11]([C:13]1[CH2:14][O:15][C:16]2[C:21]([CH:22]=1)=[CH:20][C:19]([F:23])=[CH:18][CH:17]=2)#[N:12].[OH-].[Na+]>C(OCC)C.O1CCCC1.O>[NH2:12][CH2:11][CH:13]1[CH2:22][C:21]2[C:16](=[CH:17][CH:18]=[C:19]([F:23])[CH:20]=2)[O:15][CH2:14]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 6451240Aluminum(III) ChlorideHCID 150274626-fluoro-2H-chromene-3-carbonitrileHCID 21226445Aluminium lithium hydride

Product 1

HCID 15027463(6-Fluorochroman-3-YL)methanamineYield 52.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

In an argon atmosphere, a mixture of 0.89 g (6.66 mmol) of aluminium trichloride in 40 ml of absolute diethyl ether is added dropwise while stirring at room temperature to a suspension of 1.52 g (40 mmol) of lithium aluminium hydride in 50 ml of absolute diethyl ether. Subsequently, a solution of 3.5 g (20 mmol) of 3-cyano-6-fluoro-2H-chromene in 50 ml of absolute tetrahydrofuran is added dropwise within a period of 20 minutes to the diethyl ether solution. The reaction mixture is then boiled under reflux for 16 hours. After cooling to room temperature, the reaction mixture is carefully decomposed with 1.52 ml of water, 1.52 ml of sodiumhydroxide solution (15%) and 4.6 ml of water. The resulting precipitate is filtered off with suction and the filtrate is concentrated by evaporation in vacuo. The oily residue is dissolved in diethyl ether and the etheral solution is washed with water and then extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline with sodium hydroxide solution (30%) while cooling and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulfate and concentrated by evaporation in vacuo, yielding 1.89 g of 3-aminomethyl-6-fluoro-chroman in the form of a light-yellow oil. 3-Aminomethyl-6-fluoro-chroman hydrochloride, prepared therefrom with hydrochloric acid in diethyl ether, crystallizes from methanol/acetone and has a melting range of from 208° to 211°.

Workup

  1. additionis added dropwise
  2. temperatureunder reflux for 16 hours
  3. filtrationThe resulting precipitate is filtered off with suction
  4. concentrationthe filtrate is concentrated by evaporation in vacuo
  5. dissolutionThe oily residue is dissolved in diethyl ether
  6. washthe etheral solution is washed with water
  7. extractionextracted with 2N hydrochloric acid
  8. temperaturewhile cooling
  9. extractionextracted with dichloromethane
  10. dry with materialThe combined dichloromethane phases are dried over sodium sulfate
  11. concentrationconcentrated by evaporation in vacuo

Sources & evidence

ORD record
ord-8a2fb3e5127a4f88999d3589fdde3600
Source dataset
uspto-grants-1992_05
Patent number
US05112855

Reaction notes

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