Trifluoroacetic acid → (R)-6-chloro-4-methyl-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one

HRID 11908Notes

Reaction equation

HRID 11908 reaction equation
C(OC([C:6]1[N:15]([C@H:16]([CH3:26])[CH2:17][NH:18][C:19](OC(C)(C)C)=[O:20])[C:9]2=[N:10][C:11]([Cl:14])=[CH:12][CH:13]=[C:8]2[CH:7]=1)=O)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl.O.C(OCC)(=O)C>[Cl:14][C:11]1[N:10]=[C:9]2[C:8](=[CH:13][CH:12]=1)[CH:7]=[C:6]1[N:15]2[C@H:16]([CH3:26])[CH2:17][NH:18][C:19]1=[O:20]

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 86760224(R)-1-(2-tert-Butoxycarbonylamino-1-methyl-ethyl)-6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 86590110(R)-6-chloro-4-methyl-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 6.70 g (17.5 mmol) (R)-1-(2-tert-butoxycarbonylamino-1-methyl-ethyl)-6-chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid ethyl ester in 80 ml dichloromethane was cooled to 0 deg C. and 27 ml (0.35 mol) trifluoroacetic acid were added over 4 min. The cooling bath was removed and after 1 h the volatile components were removed on a rotary evaporator. The residue was dissolved in 40 ml methanol and 9.70 g (70.2 mmol) potassium carbonate was added. After stirring for 2.5 h the reaction mixture was diluted with water and ethyl acetate and the phases were separated. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate and filtered. After evaporation, the residue was taken up in 50 ml tert-butyl methyl ether upon which the product started to precipitate. The solid was collected by filtration, washed with 20 ml of tert-butyl methyl ether and dried under high vacuum to afford the product as a pale yellow powder. The concentrated mother liquors were purified by flash chromatography over silica gel (0.032–0.063 mm) with ethyl acetate as eluant to yield another batch of product (86.6% total).

Workup

  1. customThe cooling bath was removed and after 1 h the volatile components
  2. customwere removed on a rotary evaporator
  3. dissolutionThe residue was dissolved in 40 ml methanol
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted three times with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customAfter evaporation
  10. customto precipitate
  11. filtrationThe solid was collected by filtration
  12. washwashed with 20 ml of tert-butyl methyl ether
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-c012507fc04e49d28877f9bb49e6f4c1
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Reaction notes

Loading…