Water → HCID 71495336, compound

HRID 588058Notes

Reaction equation

HRID 588058 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:18]1[N:33]=[CH:32][CH:31]=[CH:30][C:19]=1[C:20]([NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=1)=[O:21].O>CN(C)C=O.CC(=O)OCC.CCCCCC>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:18]2[N:33]=[CH:32][CH:31]=[CH:30][C:19]=2[C:20]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)=[O:21])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 784611-Benzylpiperidin-4-olHCID 1419048HCID 1419048, compound

Product 1

HCID 71495336HCID 71495336, compoundYield 59.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-benzyl-4-hydroxypiperidine (209 mg, 1.1 mmol, 1.1 eq) and 95 w % sodium hydride (1.2 mmol) in 5 ml of dimethylformamide was stirred at a room temperature for 30 min, mixed with 2-chloro-N-(3-chlorophenyl)nicotinamide (1.0 mmol), and stirred for 20 hrs under reflux. The reaction mixture was cooled to a room temperature, and added with 20 ml of pure water to terminate the reaction. After two rounds of extraction with 20 ml of ethylacetate per round, water was removed with a desiccant and the resulting product was concentrated under reduced pressure. Then, the residue obtained by the concentration was subjected to silica gel column chromatography (mobile phase: 30 (v/v) % hexane in EA) to obtain the desired fraction. The desired fraction was dried in a reduced pressure to afford 0.25 g of the title compound (Yield: 33.7%). 1H NMR (CDCl3) δ 8.60 (d, 1H), 8.29 (d, 1H), 7.88 (s, 1H), 7.48 (d, 1H), 7.36-7.27 (m, 6H), 7.17-7.05 (m, 2H), 5.51-5.38 (m, 1H), 3.59 (s, 2H), 2.89-2.80 (m, 2H), 2.42 (t, 2H), 2.29-2.23 (m, 2H), 2.06-1.87 (m, 2H) ppm.

Workup

  1. temperatureunder reflux
  2. customto terminate
  3. customthe reaction
  4. extractionAfter two rounds of extraction with 20 ml of ethylacetate per round, water
  5. customwas removed with a desiccant and the resulting product
  6. concentrationwas concentrated under reduced pressure
  7. customThen, the residue obtained by the concentration
  8. customto obtain the desired fraction
  9. customThe desired fraction was dried in a reduced pressure

Sources & evidence

ORD record
ord-136f88f3507d46f9a79de804233734b4
Source dataset
uspto-grants-2016_01
Patent number
US09227955B2

Reaction notes

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