2,2,2-Trifluoroethylamine hydrochloride → HCID 18519913, compound

HRID 1368179Notes

Reaction equation

HRID 1368179 reaction equation
CO[CH:3]1[CH2:7][CH2:6][CH:5](OC)[O:4]1.Cl.[F:11][C:12]([F:16])([F:15])[CH2:13][NH2:14].[CH2:17]([C:24](O)=O)[C:18](CC(O)=O)=O.C([O-])(=O)C.[Na+]>Cl.O.C(=O)([O-])[O-].[K+].[K+]>[F:11][C:12]([F:16])([F:15])[CH2:13][N:14]1[CH:6]2[CH2:5][CH2:24][CH:17]1[CH2:18][C:3](=[O:4])[CH2:7]2

Participants

8

Reactant 4

HCID 97722,2,2-Trifluoroethylamine hydrochlorideHCID 68328Acetonedicarboxylic acidHCID 790982,5-DimethoxytetrahydrofuranHCID 517045Sodium Acetate

Product 1

HCID 18519913HCID 18519913, compoundYield 33.7%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 962WaterSolvent2×HCID 11430Potassium CarbonateSolvent

Procedure

A few drops of dilute hydrochloric acid were added to a solution of 2,5-dimethoxytetrahydrofuran (16.5 g) in water (70 ml). After stirring at room temperature for 30 minutes 2,2,2-trifluoroethylamine hydrochloride (16.9 g), 1,3-acetonedicarboxylic acid (18.3 g) and sodium acetate (10.0 g) were added and the mixture stirred at room temperature for 2 days. The mixture was diluted to 500 ml with water, saturated with potassium carbonate and extracted with ethyl acetate (×2). The combined organic extracts were washed with aqueous potassium carbonate, dried (MgSO4) and evaporated under reduced pressure. Distillation (90° C.; 0.1 mmHg) gave 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-one (8.7 g) Potassium t-butoxide (5.4 g) was added slowly with cooling to a stirred solution of 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-one (4.0 g) and tosylmethyl isocyanide (4.9 g) in dimethoxyethane (80 ml) and ethanol (5 ml) under nitrogen at such a rate so as to keep the temperature below 10° C. The mixture was stirred for 18 hours while allowing it to warm to room temperature, evaporated under reduced pressure and added to aqueous potassium carbonate solution. The mixture was extracted with ethyl acetate (×2) and the combined extracts were dried (MgSO4) and evaporated under reduced pressure to give an oil. The mixture was extracted with refluxing hexane and the extracts allowed to cool and evaporated under reduced pressure to give exo-3-cyano-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octane (2.5 g) m.p. 90-92° C.

Workup

  1. additionwere added
  2. extractionextracted with ethyl acetate (×2)
  3. washThe combined organic extracts were washed with aqueous potassium carbonate
  4. dry with materialdried (MgSO4)
  5. customevaporated under reduced pressure
  6. distillationDistillation (90° C.; 0.1 mmHg)

Sources & evidence

ORD record
ord-f35deaa9caa14f4db70d06bca1126090
Source dataset
uspto-grants-2003_06
Patent number
US06573275B1

Reaction notes

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