Water → 4-({4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-4-oxobutanoyl}amino)benzoic acid

HRID 1691710Notes

Reaction equation

HRID 1691710 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28](=[O:44])[CH2:29][CH2:30][C:31]([NH:33][C:34]2[CH:43]=[CH:42][C:37]([C:38]([O:40]C)=[O:39])=[CH:36][CH:35]=2)=[O:32])[CH2:24][CH:23]1[C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[CH:46]=1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].C(OCC)(=O)C.O>C1COCC1.CO>[C:1]([O:5][C:6]([N:8]([CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28](=[O:44])[CH2:29][CH2:30][C:31]([NH:33][C:34]2[CH:35]=[CH:36][C:37]([C:38]([OH:40])=[O:39])=[CH:42][CH:43]=2)=[O:32])[CH2:24][CH:23]1[C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[CH:46]=1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 66905908methyl 4-({4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-4-oxobutanoyl}amino)benzoate

Product 1

HCID 669061274-({4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-4-oxobutanoyl}amino)benzoic acidYield 52.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 208 mg of methyl 4-({4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-4-oxobutanoyl}amino)benzoate in 2.0 mL of THF and 1.0 mL of methanol was added 1.00 mL of a 1 M aqueous sodium hydroxide solution at room temperature, followed by stirring at 60° C. for 2 hours. The reaction mixture was cooled to room temperature, ethyl acetate and water were added thereto, and a liquid separation operation was conducted. The obtained aqueous layer was neutralized by addition of 1.00 mL of 1 M hydrochloric acid, and then extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 107 mg of 4-({4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-4-oxobutanoyl}amino)benzoic acid as a yellow oily compound. ESI−: 680

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customa liquid separation operation
  3. additionThe obtained aqueous layer was neutralized by addition of 1.00 mL of 1 M hydrochloric acid
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationAfter filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-f191045ce0ec4b5296e7825dbdbce136
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

Loading…