Trifluoroacetic acid → HCID 86709393, compound

HRID 2172251Notes

Reaction equation

HRID 2172251 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=O.C(O[C:13]([N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][N:22]2[CH2:27][CH2:26][N:25]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH:36]4[O:41][C:40]5=[N:42][C:43]([N+:45]([O-:47])=[O:46])=[CH:44][N:39]5[CH2:38][CH2:37]4)=[CH:30][CH:29]=3)[CH2:24][CH2:23]2)[CH2:17][CH2:16]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[N+:45]([C:43]1[N:42]=[C:40]2[N:39]([CH:44]=1)[CH2:38][CH2:37][CH:36]([CH2:35][O:34][C:31]1[CH:32]=[CH:33][C:28]([N:25]3[CH2:24][CH2:23][N:22]([CH2:21][CH:18]4[CH2:19][CH2:20][N:15]([CH2:13][C:18]5[CH:19]=[CH:20][C:3]([C:2]([F:7])([F:6])[F:1])=[CH:16][CH:17]=5)[CH2:16][CH2:17]4)[CH2:27][CH2:26]3)=[CH:29][CH:30]=1)[O:41]2)([O-:47])=[O:46]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 70874855HCID 70874855, compound

Product 1

HCID 86709393HCID 86709393, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1.5 ml) was added to a methylene chloride solution (1.5 ml) of 4-{4-[4-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-ylmethoxy)phenyl]piperazin-1-ylmethyl}piperidine-1-carboxylic acid tert-butyl ester (300 mg), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, methylene chloride (1.5 ml) and triethylamine (1.5 ml) were added to the residue, and the result was stirred at room temperature for 5 minutes. After concentrating the reaction mixture under reduced pressure, methanol (3 ml), 4-(trifluoromethyl)benzaldehyde (130 mg), sodium cyanoborohydride (160 mg) and acetic acid (1 ml) were added to the residue in this order, and the mixture was stirred at room temperature overnight. The resulting reaction mixture was added to a potassium carbonate aqueous solution, followed by extraction with methylene chloride. The organic layer was washed with a saturated sodium chloride aqueous solution and dried over sodium sulfate. After filtering, the filtrate was concentrated under reduced pressure, the residue was purified by silica gel column chromatography (methylene chloride:methanol=1:0→methylene chloride:methanol=9:1) and recrystallized from methanol to afford the title compound as a pale yellow powder (50 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, methylene chloride (1.5 ml) and triethylamine (1.5 ml)
  2. additionwere added to the residue
  3. stirringthe result was stirred at room temperature for 5 minutes
  4. concentrationAfter concentrating the reaction mixture under reduced pressure, methanol (3 ml), 4-(trifluoromethyl)benzaldehyde (130 mg), sodium cyanoborohydride (160 mg) and acetic acid (1 ml)
  5. additionwere added to the residue in this order
  6. stirringthe mixture was stirred at room temperature overnight
  7. customThe resulting reaction mixture
  8. extractionfollowed by extraction with methylene chloride
  9. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  10. dry with materialdried over sodium sulfate
  11. filtrationAfter filtering
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography (methylene chloride:methanol=1:0→methylene chloride:methanol=9:1)
  14. customrecrystallized from methanol

Sources & evidence

ORD record
ord-41537d4d3f5c4814875477eac2ead0b3
Source dataset
uspto-grants-2015_06
Patent number
US09051333B2

Reaction notes

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