Acetyl chloride → HCID 91507122, compound

HRID 1242593Notes

Reaction equation

HRID 1242593 reaction equation
[CH3:1][O:2][N:3]=[C:4]1[CH2:8][C@@H:7]([C:9]2[N:13]=[C:12]([CH2:14][N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[O:11][N:10]=2)[N:6]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)=[O:22])[CH2:5]1.C(N(CC)CC)C.[C:42](Cl)(=[O:44])[CH3:43].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[CH3:1][O:2][N:3]=[C:4]1[CH2:8][C@@H:7]([C:9]2[N:13]=[C:12]([CH2:14][N:15]3[CH2:16][CH2:17][N:18]([C:42](=[O:44])[CH3:43])[CH2:19][CH2:20]3)[O:11][N:10]=2)[N:6]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)=[O:22])[CH2:5]1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 58714592HCID 58714592, compound

Product 1

HCID 91507122HCID 91507122, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution containing 1 equivalent of (3EZ,5S)-1-([1,1′-biphenyl]-4-ylcarbonyl)-5-[5-(1-piperazinylmethyl)-1,2,4-oxadiazol-3-yl]-3-pyrrolidinone O-methyloxime (Example 48) in dry DCM at 0° C. were added 1.5 equivalent of triethyl amine and 1 equivalent of acetyl chloride. The reaction mixture was stirred at this temperature for 30 minutes and then hydrolyzed with ice. The reaction was then made basic with a sodium carbonate solution (10%) and extracted with DCM. The organic phase was dried with magnesium sulfate and solvent removal afforded a residue which was purified by flash-chromatography to give the expected product, (3EZ,5S)-5-{5-[(4-acetyl-1-piperazinyl)methyl]-1,2,4-oxadiazol-3-yl}-1-([1,1′-biphenyl]-4-ylcarbonyl)-3-pyrrolidinone O-methyloxime as a mixture of E-/Z-isomers, in 70% yield (94.4% purity by HPLC). The pure Z-isomer could be separated by flash-chromatography using cyclohexane/ethylacetate (1/1) as eluent, and was obtained in 40% yield (98.0% purity by HPLC).

Workup

  1. extractionextracted with DCM
  2. dry with materialThe organic phase was dried with magnesium sulfate and solvent removal
  3. customafforded a residue which
  4. customwas purified by flash-chromatography

Sources & evidence

ORD record
ord-ee06e7bdca684b75af26b66966c2a2ca
Source dataset
uspto-grants-2006_10
Patent number
US07115639B2

Reaction notes

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