Triethylamine → HCID 66906261, compound

HRID 1691685Notes

Reaction equation

HRID 1691685 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.Cl[C:43]([O:45][C:46]1[CH:55]=[CH:54][C:49]([C:50]([O:52]C)=[O:51])=[CH:48][CH:47]=1)=[O:44]>C1COCC1>[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]([O:45][C:46]2[CH:55]=[CH:54][C:49]([C:50]([OH:52])=[O:51])=[CH:48][CH:47]=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

5

Reactant 3

HCID 8471TriethylamineHCID 854163Methyl 4-[(chlorocarbonyl)oxy]benzoateHCID 59178632HCID 59178632, compound

Product 1

HCID 66906261HCID 66906261, compoundYield 95.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 300 mg of tert-butyl {[4-(3-fluorophenyl)piperidin-3-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate in 2 mL of THF were added 0.136 mL of triethylamine and 167 mg of methyl 4-[(chlorocarbonyl)oxy]benzoate (Fluka), followed by stirring at room temperature for 2 hours. It was washed with water, and extracted with ethyl acetate, and the organic layer was then 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, 8 mL of isopropanol, and 4 mL of a 1 M aqueous sodium hydroxide solution, followed by stirring at room temperature for 2 days. After neutralizing by addition of 4.1 mL of 1 M hydrochloric acid, the reaction mixture was concentrated under reduced pressure. The obtained residue was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 387 mg of 4-({[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(3-fluorophenyl)piperidin-1-yl]carbonyl}oxy)benzoic acid as a colorless foamy substance. ESI+: 627

Workup

  1. washIt was washed with water
  2. extractionextracted with ethyl acetate
  3. washthe organic layer was then 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, 8 mL of isopropanol, and 4 mL of a 1 M aqueous sodium hydroxide solution
  8. stirringby stirring at room temperature for 2 days
  9. additionAfter neutralizing by addition of 4.1 mL of 1 M hydrochloric acid
  10. concentrationthe reaction mixture was concentrated under reduced pressure
  11. extractionThe obtained residue was extracted with chloroform
  12. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  13. filtrationAfter filtration
  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-5025101e37284ef0b27becb6a2de4a34
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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