Water → HCID 22466780, compound

HRID 1934373Notes

Reaction equation

HRID 1934373 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([CH:19]3[CH2:24][CH2:23][N:22]([CH2:25][CH3:26])[CH2:21][CH2:20]3)=[CH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C(Cl)(=[O:29])C.O>C(Cl)Cl.[OH-].[Na+]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([CH:19]3[CH2:24][CH2:23][N:22]([C:25](=[O:29])[CH3:26])[CH2:21][CH2:20]3)=[CH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 6367Acetyl chlorideHCID 15550445HCID 15550445, compound

Product 1

HCID 22466780HCID 22466780, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

An alternative procedure to prepare compound B from compound A is as follows: Compound A (1.0 g) in 25 ml dry methylene chloride and 10 ml of 2.5 N NaOH was cooled to 0° C. and treated with 0.25 ml of acetyl chloride dropwise. After 2 hours the solution was allowed to warm up to room temperature and stirring was continued overnight. The solution was treated with distilled water and extracted with methylene chloride. The methylene chloride layer was separated, dried over anhydrous sodium sulfate, filtered and evapotated to give 1.33 g of crude amide reaction product, which was purified by flash column (silica, methylene chloride:methanol:25% NH4OH 90:9:1) to yield 0.7 g of 2-(4-fluorophenyl)-5-(N-acetylpiperidin-4-yl)-3-(4-pyridyl)pyrrole. This amide was dissolved in 15 ml of tetrahydrofuran and treated with 3 ml of 1M lithium aluminum hydride (LAH) in THF under an atmosphere of nitrogen at room temperature. After completion of addition of LAH, the solution was refluxed for two hours, cooled to 0° C., quenched with water (0.19 ml) and 2.5 N NaOH (0.19 ml) and filtered. The filtrate was dried over sodium sulfate, filtered, evaporated and purified by flash column as shown above to give compound B (0.65 g).

Workup

  1. waitwas continued overnight
  2. extractionextracted with methylene chloride
  3. customThe methylene chloride layer was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customto give
  7. customwas purified by flash column (silica, methylene chloride:methanol:25% NH4OH 90:9:1)

Sources & evidence

ORD record
ord-34e1386009b64aeb9551e262811b6a1a
Source dataset
uspto-grants-2002_05
Patent number
US06384052B1

Reaction notes

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