(2S)-N2-(1-benzhydryl-3-azetanyl)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxamide → (2S)-1-(1,3-benzoxazol-2-yl)-N2-(1-ethyl-3-azetanyl)-2-piperidinecarboxamide

HRID 841926Notes

Reaction equation

HRID 841926 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([NH:18][C:19]([C@@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][N:22]2[C:27]2[O:28][C:29]3[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=3[N:31]=2)=[O:20])[CH2:15]1)(C1C=CC=CC=1)[C:2]1C=CC=CC=1>C(O)C.[OH-].[OH-].[Pd+2]>[O:28]1[C:29]2[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=2[N:31]=[C:27]1[N:22]1[CH2:23][CH2:24][CH2:25][CH2:26][C@H:21]1[C:19]([NH:18][CH:16]1[CH2:17][N:14]([CH2:1][CH3:2])[CH2:15]1)=[O:20]

Participants

4

Reactant 1

HCID 57139910(2S)-N2-(1-benzhydryl-3-azetanyl)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxamide

Product 1

HCID 57191767(2S)-1-(1,3-benzoxazol-2-yl)-N2-(1-ethyl-3-azetanyl)-2-piperidinecarboxamideYield 43.9%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst2×HCID 702EthanolSolvent

Procedure

20% w/w Palladium hydroxide on carbon (31 mg) was added to a solution of (2S)-N2-(1-benzhydryl-3-azetanyl)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxamide (120 mg) [see Example 28] in ethanol (5 ml). The reaction mixture was hydrogenated for 18 hours at 414 kPa (60 p.s.i.), after which time additional 20% w/w palladium hydroxide on carbon (32 mg) was added and the mixture hydrogenated for a further 72 hours. The catalyst was then filtered off and washed with ethanol and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 100:0 changing to 90:10, by volume, dichloromethane:methanol in 2% increments, to afford (2S)-1-(1,3-benzoxazol-2-yl)-N2-(1-ethyl-3-azetanyl)-2-piperidinecarboxamide (37.1 mg) as a foam.

Workup

  1. waitthe mixture hydrogenated for a further 72 hours
  2. filtrationThe catalyst was then filtered off
  3. washwashed with ethanol
  4. customthe solvent was removed under reduced pressure
  5. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 100:0 changing to 90:10, by volume, dichloromethane

Sources & evidence

ORD record
ord-10b540a20a304c1fb47b8bb0969f1127
Source dataset
uspto-grants-2002_04
Patent number
US06372736B1

Reaction notes

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