Trifluoroacetic acid → 6-Hydroxy-10-(8-phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid diethylamide

HRID 2117041Notes

Reaction equation

HRID 2117041 reaction equation
C(O)(C(F)(F)F)=O.[CH2:8]([N:10]([CH2:45][CH3:46])[C:11]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:29]3[CH2:35][CH:34]4[N:36]([CH2:37][CH2:38][C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)[CH:31]([CH2:32][CH2:33]4)[CH2:30]3)[C:18]3[C:23]([O:24][C:25]=2[CH:26]=1)=[C:22]([O:27]C)[CH:21]=[CH:20][CH:19]=3)=[O:12])[CH3:9].B(Br)(Br)Br.C([O-])(O)=O.[Na+]>>[CH2:45]([N:10]([CH2:8][CH3:9])[C:11]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:29]3[CH2:30][CH:31]4[N:36]([CH2:37][CH2:38][C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)[CH:34]([CH2:33][CH2:32]4)[CH2:35]3)[C:18]3[C:23]([O:24][C:25]=2[CH:26]=1)=[C:22]([OH:27])[CH:21]=[CH:20][CH:19]=3)=[O:12])[CH3:46]

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 116709266-methoxy-10-(8-phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid diethylamide2×

Product 1

HCID 115480096-Hydroxy-10-(8-phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid diethylamideYield 42.8%

Procedure

To a solution of the TFA salt of 6-methoxy-10-(8-phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid diethylamide, 6e (55 mg, 0.086 mmol) in 1,2-dichloromethane (5 mL) at 0° C. was added a 1M solution of BBr3 (0.43 mL, 0.43 mmol). The mixture was allowed to stir for 2 h at rt. A saturated NaHCO3 solution was added, and the organic phase was separated. The aqueous phase was extracted with methylene chloride, and the combined organic phases were dried, filtered, and evaporated. The residue was purified via reverse phase HPLC (eluent: CH3CN in water containing 0.1% TFA) to yield 23 mg (42.8%) of title compound 6-hydroxy-10-(8-phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-10H-phenoxazine-3-carboxylic acid diethylamide, 7e as a TFA salt and as a mixture of endo and exo isomers. MS m/z=512 (M+1).

Workup

  1. customthe organic phase was separated
  2. extractionThe aqueous phase was extracted with methylene chloride
  3. customthe combined organic phases were dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified via reverse phase HPLC (eluent: CH3CN in water containing 0.1% TFA)

Sources & evidence

ORD record
ord-b5109517ba004d048ef207b7a163a596
Source dataset
uspto-grants-2008_10
Patent number
US07439239B2

Reaction notes

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