Hydrochloric Acid → HCID 68325405, compound

HRID 2403274Notes

Reaction equation

HRID 2403274 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][CH:20]([C:25]3[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][N:26]=3)[C:21]([F:24])([F:23])[F:22])=[CH:15][CH:14]=2)[CH2:9]1)=O)(C)(C)C.Cl>C1COCC1.O1CCOCC1.C(OCC)(=O)C.C1COCC1>[Br:31][C:28]1[CH:29]=[CH:30][C:25]([CH:20]([NH:19][C:16]2[CH:17]=[CH:18][C:13]([CH:10]3[CH2:11][CH2:12][NH:8][CH2:9]3)=[CH:14][CH:15]=2)[C:21]([F:22])([F:24])[F:23])=[N:26][CH:27]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 68325504HCID 68325504, compound

Product 1

HCID 68325405HCID 68325405, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of (RS)-3-{4-[(RS)-1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethylamino]-phenyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (27 mg) in THF (1 ml) was added dropwise a solution of hydrogen chloride in dioxane (0.20 ml, 4 M solution) and the mixture was heated at 60° C. for 4 hours. The mixture was then cooled to room temperature, diluted with ethyl acetate/THF (1:1), and washed sequentially with 2 N aq. sodium hydroxide solution and with saturated brine. The organic phase was separated, dried over sodium sulphate, and concentrated in vacuo. The reside was purified by flash column chromatography (silical gel; gradient: heptane/dichloromethane/methanol) to give [(RS)-1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethyl]-((RS)-4-pyrrolidin-3-yl-phenyl)-amine (12 mg, 56%) as a yellow amorphous solid. MS (ISP): 402.1 ([{81Br}M+H]+), 400.1 ([{79Br}M+H]+).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. washwashed sequentially with 2 N aq. sodium hydroxide solution and with saturated brine
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe reside was purified by flash column chromatography (silical gel; gradient: heptane/dichloromethane/methanol)

Sources & evidence

ORD record
ord-190b30c02a0040959a48acf4c7518b84
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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