Trifluoroacetic acid → (R)-8-hydroxy-4-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

HRID 2105338Notes

Reaction equation

HRID 2105338 reaction equation
C(OC([C:6]1[N:7]([C@H:23]([CH3:33])[CH2:24][NH:25][C:26](OC(C)(C)C)=[O:27])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][Si](C(C)(C)C)(C)C)=[CH:10][CH:9]=2)=O)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl.O.C(OCC)(=O)C>[OH:15][C:11]1[CH:10]=[CH:9][C:8]2[N:7]3[C@H:23]([CH3:33])[CH2:24][NH:25][C:26](=[O:27])[C:6]3=[CH:14][C:13]=2[CH:12]=1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 684627241-((R)-2-tert-butoxycarbonylamino-1-methyl-ethyl)-5-(tert-butyl-dimethyl-silanyloxy)-1H-indole-2-carboxylic acid ethyl ester

Product 1

HCID 68465924(R)-8-hydroxy-4-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-oneYield 57%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The solution of 0.60 g (1.26 mmol) 1-((R)-2-tert-butoxycarbonylamino-1-methyl-ethyl)-5-(tert-butyl-dimethyl-silanyloxy)-1H-indole-2-carboxylic acid ethyl ester in 8 mL dichloromethane was cooled to 0° C. and 1.9 mL (2.8 g, 24.9 mmol) trifluoroacetic acid was added dropwise within 5 min. The cooling bath was removed and after 1.5 hours the volatile components were removed at a rotary evaporator. The residue was dissolved in methanol, cooled to 0° C. and 0.69 g (5.0 mmol) potassium carbonate was added. The suspension was stirred for 6 hours at room temperature, diluted with water and ethyl acetate and the layers were separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The crude product was purified by flash column chromatography on silica gel with ethyl acetate as eluant to give 0.15 g (57%) of the desired product as a light brown gum.

Workup

  1. customThe cooling bath was removed and after 1.5 hours the volatile components
  2. customwere removed at a rotary evaporator
  3. dissolutionThe residue was dissolved in methanol
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted twice with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by flash column chromatography on silica gel with ethyl acetate as eluant

Sources & evidence

ORD record
ord-1f994d7d74074e5d92f49251e533b0d6
Source dataset
uspto-grants-2009_08
Patent number
US07579351B2

Reaction notes

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