Hydrochloric Acid → 1-(3-fluorophenyl)ethanamine

HRID 2041205Notes

Reaction equation

HRID 2041205 reaction equation
C([BH3-])#[N:2].[Na+].[CH3:5][C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=1)=O.C([O-])(=O)C.[NH4+].Cl>CO.C(OCC)C>[F:14][C:10]1[CH:9]=[C:8]([CH:6]([NH2:2])[CH3:5])[CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 99673-FluoroacetophenoneHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 27823621-(3-fluorophenyl)ethanamine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

Add sodium cyanoborohydride (452 mg, 7.2 mmol) to a solution of 3-fluoroacetophenone (500 mg, 3.6 mmol) and ammonium acetate (2.8 g, 36 mmol) in methanol (11 mL). Stir the mixture for 96 h at ambient temperature under a nitrogen atmosphere. Adjust to pH 2 with 2M hydrogen chloride in diethyl ether. Concentrate the slurry in vacuo, dilute the residue with DCM and wash with 5N aqueous NaOH followed by saturated aqueous NaHCO3. Dry the organic layer, concentrate in vacuo to half of the volume, and load the solution onto a SCX column (pre-wash column with methanol followed by DCM, then elute with 2M ammonia in methanol). Concentrate the fractions to half of the volume to remove ammonia, add excess of 2M hydrogen chloride in diethyl ether and concentrate to obtain the hydrochloride salt (70:30 mixture of title compound and dimer). Purify by chromatography on silica gel eluting with DCM/2M ammonia in methanol (20:1) to obtain the title compound (323 mg, 51%). MS (ES+) m/z: 140 (M+H)+

Workup

  1. concentrationConcentrate the slurry in vacuo
  2. additiondilute the residue with DCM
  3. washwash with 5N aqueous NaOH
  4. customDry the organic layer
  5. concentrationconcentrate in vacuo to half of the volume, and load the solution onto a SCX column (
  6. washpre-wash column with methanol
  7. washelute with 2M ammonia in methanol)
  8. concentrationConcentrate the fractions to half of the volume
  9. customto remove ammonia
  10. additionadd excess of 2M hydrogen chloride in diethyl ether
  11. concentrationconcentrate

Sources & evidence

ORD record
ord-2133b027bddb4227ac608eacb8d61376
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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