Acetyl chloride → Ammonia

HRID 2119372Notes

Reaction equation

HRID 2119372 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[O:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]1[C:20]([NH:22][CH2:23][CH2:24][N:25]1[C@H:30]([CH3:31])[CH2:29][NH:28][CH2:27][C@@H:26]1[CH3:32])=[O:21].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH3:7].[C:1]([N:28]1[CH2:27][C@@H:26]([CH3:32])[N:25]([CH2:24][CH2:23][NH:22][C:20]([C@@H:15]2[CH2:16][CH2:17][CH2:18][CH2:19][N:14]2[C:6]2[O:5][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[N:7]=2)=[O:21])[C@@H:30]([CH3:31])[CH2:29]1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 11430Potassium CarbonateHCID 9821522(2S)-1-(1,3-benzoxazol-2-yl)-N2-2-[(cis)-2,6-dimethyl-1-piperazinyl]ethyl-2-piperidinecarboxamide

Product 2

HCID 222AmmoniaHCID 9954262(2S)-N2-2-[(cis)-4-acetyl-2,6-dimethyl-1-piperazinyl]ethyl-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Acetyl chloride (0.018 ml) was added to a solution of (2S)-1-(1,3-benzoxazol-2-yl)-N2-2-[(cis)-2,6-dimethyl-1-piperazinyl]ethyl-2-piperidinecarboxamide (0.1 g) [see Example 8] and potassium carbonate (36 mg) in acetonitrile (2 ml). The reaction mixture was stirred at room temperature for 2 hours, after which time the solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and water. The organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 97:3.5:0.5 changing to 97:3:1, by volume, dichloromethane:methanol:0.88 aqueous ammonia solution (93:7:1), to afford (2S)-N2-2-[(cis)-4-acetyl-2,6-dimethyl-1-piperazinyl]ethyl-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxamide (91.6 mg) as a white foam.

Workup

  1. customafter which time the solvent was removed under reduced pressure
  2. customthe residue partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulphate
  5. customthe solvent removed under reduced pressure
  6. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 97:3.5:0.5 changing to 97:3:1, by volume, dichloromethane

Sources & evidence

ORD record
ord-f63a1ac35cc24afaa1655299a88cc552
Source dataset
uspto-grants-2004_02
Patent number
US06686357B1

Reaction notes

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