Ethyl Acetate → 1-((4'-Chlorobiphenyl-2-yl)methyl)-3-fluoropiperidin-4-one

HRID 2406238Notes

Reaction equation

HRID 2406238 reaction equation
[F:1][CH:2]1[C:7](=[O:8])[CH2:6][CH2:5][NH:4][CH2:3]1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22]I)=[CH:12][CH:11]=1.CCN(C(C)C)C(C)C.CCOC(C)=O>CN(C=O)C>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22][N:4]2[CH2:5][CH2:6][C:7](=[O:8])[CH:2]([F:1])[CH2:3]2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 252105113-Fluoropiperidin-4-oneHCID 670542934'-Chloro-2-(iodomethyl)biphenyl

Product 1

HCID 670544011-((4'-Chlorobiphenyl-2-yl)methyl)-3-fluoropiperidin-4-oneYield 87.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-Fluoro-piperidin-4-one (0.32 g, 2.7 mmol) was dissolved in DMF (13 mL) and 4′-chloro-2-(iodomethyl)biphenyl (1.03 g, 3.13 mmol) was added followed by DIPEA (1.06 g, 8.2 mmol). The reaction was stirred at ambient temperature for 16 hours, and then poured into EtOAc (100 mL). The organics were washed with water followed by brine, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography on silica gel afforded the title compound (0.75 g, 86% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.47-7.59 (m, 1H), 7.21-7.47 (m, 7H), 4.72-5.00 (m, 1H), 3.62-3.65 (d, J=12 Hz, 1H), 3.56-3.59 (d, J=12 Hz, 1H), 3.25-3.42 (m, 1H), 2.88-3.06 (m, 1H), 2.28-2.63 (m, 4H).

Workup

  1. washThe organics were washed with water
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-1305c2eb2e2c4450916b95a6b2d6b1a1
Source dataset
uspto-grants-2014_08
Patent number
US08809352B2

Reaction notes

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