Hydrochloric Acid → 3-Fluoro-1-(1-tosyl-5-imidazolyl)propan-2-ol

HRID 27612Notes

Reaction equation

HRID 27612 reaction equation
[F:1][CH2:2][C:3]([CH2:5][C:6]1[N:10]([S:11]([C:14]2[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH:9]=[N:8][CH:7]=1)=[O:4].[BH4-].[Na+].Cl>CO>[F:1][CH2:2][CH:3]([OH:4])[CH2:5][C:6]1[N:10]([S:11]([C:14]2[CH:15]=[CH:16][C:17]([CH3:18])=[CH:19][CH:20]=2)(=[O:13])=[O:12])[CH:9]=[N:8][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 23343259HCID 23343259, compound

Product 1

HCID 233432033-Fluoro-1-(1-tosyl-5-imidazolyl)propan-2-ol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 20 mmole of 1-tosyl-5-imidazolylmethyl fluoromethyl ketone in 25 ml of methanol cooled to -10° C. is treated with 30 mg of sodium borohydride. After two hours at from -10° to 0° C. the reaction mixture is neutralized with 6 M HCl and concentrated under vacuo. The residue is extracted several times with chloroform. Evaporation of the solvent affords an oil which is purified by distillation under high vacuum to give 3-fluoro-1-(1-tosyl-5-imidazolyl)propan-2-ol. A solution of 2 g of 3-fluoro-1-(1-tosyl-5-imidazolyl)propan-2-ol, 1.37 g of phthalimide, 1.74 g of diethylazodicarboxylate in 2.4 g of triphenylphosphine and 25 ml of tetrahydrofuran is stirred under nitrogen at 25° C. for 20 hours after which the solvent is evaporated at reduced pressure and the residue is taken up in benzene. The insoluble material is discarded and the semi-solid residue obtained after concentration of the filtrate under vacuum is recrystallized using dichloromethane/diethylether to give the fluorophthalimide derivative. A solution of 1.12 g of the fluorophthalimide derivative in 0.18 g of hydrazine hydrate in 42 ml of absolute ethanol is heated at reflux for 5 hours. Upon cooling the solution is concentrated under vacuum to a volume of 15 ml, allowed to stand overnight at 0° C. then filtered. The filtrate is concentrated and distilled under high vacuum to afford 1-fluoromethyl-2-(1-tosyl-5-imidazolyl)ethylamine which is combined with 6 ml of 47% hydrogen bromide and heated under nitrogen at 100° C. for 4 hours then concentrated under reduced pressure to give a solid residue. The residue is recrystallized from ethanol-diethylether to give 1-fluoromethyl-2-(5-imidazolyl)ethylamine hydrobromide.

Workup

  1. concentrationconcentrated under vacuo
  2. extractionThe residue is extracted several times with chloroform
  3. customEvaporation of the solvent
  4. customaffords an oil which
  5. distillationis purified by distillation under high vacuum

Sources & evidence

ORD record
ord-e96477738df4447794aab557f784e5f7
Source dataset
uspto-grants-1980_09
Patent number
US04221914

Reaction notes

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