Water → HCID 66906192, compound

HRID 1691688Notes

Reaction equation

HRID 1691688 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH:9]2[CH2:14][N:15]([C@@H:23]([C:25]2[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH:28]=[CH:27][CH:26]=2)[CH3:24])[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[N:42]([C:45]1[CH:55]=[CH:54][C:48]([C:49]([O:51]CC)=[O:50])=[CH:47][CH:46]=1)=[C:43]=[O:44].O>C1(C)C=CC=CC=1>[C:18]([O:17][C:16]([N:15]([CH2:14][CH:9]1[CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH2:13][CH2:12][N:11]([C:43]([NH:42][C:45]2[CH:55]=[CH:54][C:48]([C:49]([OH:51])=[O:50])=[CH:47][CH:46]=2)=[O:44])[CH2:10]1)[C@@H:23]([C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1)[CH3:24])=[O:22])([CH3:19])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 589805Ethyl 4-isocyanatobenzoateHCID 59178632HCID 59178632, compound

Product 1

HCID 66906192HCID 66906192, compoundYield 87.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 300 mg of tert-butyl {[4-(3-fluorophenyl)piperidin-3-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate in 3.0 mL of toluene was added 0.136 mL of triethylamine and 149 mg of ethyl 4-isocyanatobenzoate at room temperature, followed by stirring at 100° C. for 2 days. The reaction mixture was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and to the obtained residue were added 8 mL of THF, 4 mL of methanol, and 4 mL of a 1 M aqueous sodium hydroxide solution, followed by stirring at room temperature for 24 hours. The reaction mixture was neutralized by addition of 4.1 mL of 1 M hydrochloric acid, then concentrated under reduced pressure, and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 356 mg of 4-({[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(3-fluorophenyl)piperidin-1-yl]carbonyl}amino)benzoic acid as a colorless foamy substance. ESI+: 626

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. additionto the obtained residue were added 8 mL of THF, 4 mL of methanol, and 4 mL of a 1 M aqueous sodium hydroxide solution
  8. stirringby stirring at room temperature for 24 hours
  9. additionThe reaction mixture was neutralized by addition of 4.1 mL of 1 M hydrochloric acid
  10. concentrationconcentrated under reduced pressure
  11. extractionextracted with chloroform
  12. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. customthe residue was purified by silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-6d3233b2ebdc4321928280444ae9c245
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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