Trifluoroacetic acid → 10-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid methyl ester

HRID 1994437Notes

Reaction equation

HRID 1994437 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][O:9][C:10](=[O:28])[C:11]1[CH:16]=[CH:15][C:14]([NH:17][CH:18]2[CH2:24][CH:23]3[N:25]([CH3:26])[CH:20]([CH2:21][CH2:22]3)[CH2:19]2)=[C:13]([OH:27])[CH:12]=1.F[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[N+]([O-])=O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:8][O:9][C:10]([C:11]1[CH:16]=[CH:15][C:14]2[N:17]([CH:18]3[CH2:19][CH:20]4[N:25]([CH3:26])[CH:23]([CH2:22][CH2:21]4)[CH2:24]3)[C:30]3[C:35]([O:27][C:13]=2[CH:12]=1)=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:28]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 738951-Fluoro-2-nitrobenzeneHCID 598146783-Hydroxy-4-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylamino)-benzoic acid methyl ester2×

Product 1

HCID 5981467610-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid methyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of the TFA salt of 3-hydroxy-4-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylamino)-benzoic acid methyl ester, 1a (0.424 g, 0.734 mmol), 2-fluoronitrobenzene (95 μL, 0.9 mmol) and potassium carbonate (564 mg, 4 mmol) in DMF was heated to reflux for 70 min. The mixture was allowed to cool to rt, filtered, and purified via reverse phase HPLC to yield 440 mg (88%) of 10-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid methyl ester, 2a, as TFA salt. MS m/z (MH+) 365.1.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 70 min
  3. filtrationfiltered
  4. custompurified via reverse phase HPLC

Sources & evidence

ORD record
ord-cfe1e61a0a91495e9a78e4e83218672e
Source dataset
uspto-grants-2010_01
Patent number
US07652005B2

Reaction notes

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