Hydrochloric Acid → 9-(4-aminopiperidine-1-yl)-5-[3,5-bis(trifluoromethyl)benzyl]-6-oxo-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine

HRID 1795813Notes

Reaction equation

HRID 1795813 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]1[CH2:14][CH2:13][CH2:12][O:11][C:10]2[N:15]=[C:16](Cl)[CH:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:9]=2[C:8]1=[O:26].C(OC([NH:43][CH:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1)=O)(C)(C)C.O.Cl>C(OCC)(=O)C>[NH2:43][CH:44]1[CH2:49][CH2:48][N:47]([C:16]2[CH:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:9]3[C:8](=[O:26])[N:7]([CH2:6][C:5]4[CH:4]=[C:3]([C:2]([F:35])([F:34])[F:1])[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=4)[CH2:14][CH2:13][CH2:12][O:11][C:10]=3[N:15]=2)[CH2:46][CH2:45]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 7238334-(N-Boc-amino)piperidineHCID 221793335-[3,5-bis(trifluoromethyl)benzyl]-9-chloro-6-oxo-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine

Product 1

HCID 221793539-(4-aminopiperidine-1-yl)-5-[3,5-bis(trifluoromethyl)benzyl]-6-oxo-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocineYield 78%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
140 °C

Procedure

A mixture of 5-[3,5-bis(trifluoromethyl)benzyl]-9-chloro-6-oxo-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine (40.0 mg) and 4-(t-butoxycarbonylamino)piperidine (38.9 mg) was stirred at 140° C. for 5 hours. To the remaining product, water was added and the mixture was extracted with ethyl acetate, followed by drying on anhydrous sodium sulfate. The solvent was then removed to obtain a residue. To this residue, a 3 mol/L ethyl acetate solution of hydrogen chloride (1 mL) was added and the mixture was stirred at room temperature for 1 hour. The solvent was again removed to obtain a residue. To this residue, ethyl acetate was added and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate, followed by drying on anhydrous sodium sulfate. The solvent was then removed and the resulting residue was purified on a silica gel column chromatography (ethyl acetate:methanol=3:1) to obtain 9-(4-aminopiperidine-1-yl)-5-[3,5-bis(trifluoromethyl)benzyl]-6-oxo-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine (35.0 mg, 78%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialby drying on anhydrous sodium sulfate
  3. customThe solvent was then removed
  4. customto obtain a residue
  5. stirringthe mixture was stirred at room temperature for 1 hour
  6. customThe solvent was again removed
  7. customto obtain a residue
  8. washthe mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate
  9. dry with materialby drying on anhydrous sodium sulfate
  10. customThe solvent was then removed
  11. customthe resulting residue was purified on a silica gel column chromatography (ethyl acetate:methanol=3:1)

Sources & evidence

ORD record
ord-fefadef355ca4d84986fc95b971440ef
Source dataset
uspto-grants-2006_04
Patent number
US07030107B2

Reaction notes

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