2-Piperidone → 4-[(4E)-3-(4-Carboxybenzyl)-5-(2-{[5-(2-oxopiperidin-1-yl)pentyl]oxy}phenyl)pent-4-en-1-yl]-benzoic acid

HRID 1512227Notes

Reaction equation

HRID 1512227 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C:2]1=[O:7].[H-].[Na+].Cl[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1/[CH:23]=[CH:24]/[CH:25]([CH2:38][C:39]1[CH:44]=[CH:43][C:42]([C:45]([O:47]C)=[O:46])=[CH:41][CH:40]=1)[CH2:26][CH2:27][C:28]1[CH:37]=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][CH:29]=1.[Cl-].[NH4+]>CN(C=O)C>[C:45]([C:42]1[CH:41]=[CH:40][C:39]([CH2:38][CH:25](/[CH:24]=[CH:23]/[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[O:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][C:2]2=[O:7])[CH2:26][CH2:27][C:28]2[CH:37]=[CH:36][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=2)=[CH:44][CH:43]=1)([OH:47])=[O:46]

Participants

6

Reactant 4

HCID 126652-PiperidoneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59437417Methyl 4-{(4E)-5-{2-[(5-chloropentyl)oxy]phenyl}-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate

Product 1

HCID 594374154-[(4E)-3-(4-Carboxybenzyl)-5-(2-{[5-(2-oxopiperidin-1-yl)pentyl]oxy}phenyl)pent-4-en-1-yl]-benzoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 19.0 mg (0.191 mmol) of 2-piperidinone [CAS Reg. No. 675-20-7] is initially charged in 1.0 ml of dry DMF, and 7.9 mg (0.197 mmol) of sodium hydride (60% in paraffin oil) are added. The mixture is stirred at room temperature for 45 min. The reaction solution is then cooled to 0° C., and a solution of 30 mg (0.056 mmol) of methyl 4-{(4E)-5-{2-[(5-chloro-pentyl)oxy]phenyl}-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate (racemate; Example 32A) in 1.5 ml of dry DMF is added. The mixture is stirred at room temperature for 1.5 h. The reaction solution is then carefully poured into 15 ml of ice-cold 10% strength ammonium chloride solution. The mixture is extracted twice with dichloromethane. The combined organic phases are dried over sodium sulfate, filtered and concentrated. The residue obtained is purified by preparative HPLC. This gives 1.9 mg (3.25 μmol, 6.0% of theory) of the title compound.

Workup

  1. temperatureThe reaction solution is then cooled to 0° C.
  2. stirringThe mixture is stirred at room temperature for 1.5 h
  3. extractionThe mixture is extracted twice with dichloromethane
  4. dry with materialThe combined organic phases are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue obtained
  8. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-afc6aa6c7db740949b24479e31506221
Source dataset
uspto-grants-2012_07
Patent number
US08217063B2

Reaction notes

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