Benzene, 1,2-dichloro-4-iodo- → HCID 66763886, compound

HRID 2167506Notes

Reaction equation

HRID 2167506 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:27]=[CH:28][CH:29]=1)[CH2:20][N:21]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22]1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:23]2([OH:26])[CH2:24][CH2:25][N:21]([CH2:20][C:19]3[CH:27]=[CH:28][CH:29]=[C:17]([O:16][CH3:15])[CH:18]=3)[CH2:22]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 88591Benzene, 1,2-dichloro-4-iodo-HCID 23053108HCID 23053108, compoundHCID 178418365HCID 178418365, compound

Product 1

HCID 66763886HCID 66763886, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 3,4-dichloro-1-iodobenzene (1.33 g, 4.90 mmol) in tetrahydrofuran (10 mL) at room temperature, was added isopropylmagnesium bromide (2.4 mL of a 2.0 M solution in THF, 4.9 mmol) dropwise. After 2 h, a solution of 1-(3-methoxybenzyl)pyrrolidin-3-one (500 mg, 2.43 mmol) from Step B above in tetrahydrofuran (3 mL) was added dropwise at 0° C. The reaction mixture was warmed to ambient temperature and stirred for 2 h. The reaction mixture was quenched with saturated ammonium chloride (5 mL). The mixture was diluted with ethyl acetate (100 mL) and washed with saturated ammonium chloride (20 mL), water (20 mL), and brine (20 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by silica gel chromatography (5% ethyl acetate/methylene chloride to 80% ethyl acetate/methylene chloride) gave 3-(3,4-dichlorophenyl)-1-(3-methoxybenzyl)pyrrolidin-3-ol (500 mg, 58%) as a yellow oil: ESI MS (m/z) 352 [M+H]+.

Workup

  1. customThe reaction mixture was quenched with saturated ammonium chloride (5 mL)
  2. additionThe mixture was diluted with ethyl acetate (100 mL)
  3. washwashed with saturated ammonium chloride (20 mL), water (20 mL), and brine (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel chromatography (5% ethyl acetate/methylene chloride to 80% ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-2bfdfbc4c0fb4a42a6e077ef9cf159f6
Source dataset
uspto-grants-2015_06
Patent number
US09045468B2

Reaction notes

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