Benzene, 1,2-dichloro-4-iodo- → HCID 66764123, compound

HRID 2167515Notes

Reaction equation

HRID 2167515 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](I)[CH:5]=[CH:6][C:7]=1[Cl:8].C([Mg]Br)(C)C.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:28]=[CH:29][CH:30]=1)[CH2:20][N:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:24]2([OH:27])[CH2:23][CH2:22][N:21]([CH2:20][C:19]3[CH:28]=[CH:29][CH:30]=[C:17]([O:16][CH3:15])[CH:18]=3)[CH2:26][CH2:25]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 88591Benzene, 1,2-dichloro-4-iodo-HCID 119595401-[(3-Methoxyphenyl)methyl]piperidin-4-oneHCID 178418365HCID 178418365, compound

Product 1

HCID 66764123HCID 66764123, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To 3,4-dichloro-1-iodobenzene (9.00 g, 41.0 mmol) in tetrahydrofuran (80 mL) at room temperature, was added isopropylmagnesium bromide (40.5 mL of a 2.0 M solution in THF, 82.0 mmol) dropwise. After 2 h, a solution of 1-(3-methoxybenzyl)piperidin-4-one (9.0 g, 41.0 mmol) from Step B above in tetrahydrofuran (10 mL) was added dropwise at 0° C. The reaction mixture was warmed to ambient temperature and stirred for 2 h. After 1 h, the reaction mixture was quenched with saturated ammonium chloride (5 mL). The mixture was diluted with ethyl acetate (50 mL) and washed with saturated ammonium chloride (80 mL), water (80 mL), brine (80 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by silica gel chromatography (dichloromethane to 10% ethyl acetate in dichloromethane) gave 4-(3,4-dichlorophenyl)-1-(3-methoxybenzyl)piperidin-4-ol (13.0, 86%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 7.62 (d, J=2.0 Hz, 1H), 7.43-7.38 (m, 1H), 7.36-7.30 (m, 1H), 7.25-7.21 (m, 1H), 6.96-6.90 (m, 2H), 6.84-6.77 (m, 1H), 3.82 (s, 3H), 3.55 (s, 2H), 2.84-2.76 (m, 2H), 2.47-2.37 (m, 2H), 2.10 (dt, J=4.5, 13.1 Hz, 2H), 1.72-1.65 (m, J=11.5 Hz, 2H); ESI MS (m/z) 366 [M+H]+.

Workup

  1. waitAfter 1 h
  2. customthe reaction mixture was quenched with saturated ammonium chloride (5 mL)
  3. additionThe mixture was diluted with ethyl acetate (50 mL)
  4. washwashed with saturated ammonium chloride (80 mL), water (80 mL), brine (80 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification by silica gel chromatography (dichloromethane to 10% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-ef1fcf07a4104bfc87b63b62b93bde88
Source dataset
uspto-grants-2015_06
Patent number
US09045468B2

Reaction notes

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