Water → 2-(2-Chloro-5-methoxy-phenyl)-1-(2-chloro-pyridin-4-yl)-propan-1-ol

HRID 1095949Notes

Reaction equation

HRID 1095949 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[Cl-].[Li+].[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[CH:25]([CH3:28])[CH:26]=[O:27].O>C1COCC1>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[CH:25]([CH3:28])[CH:26]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=1)[OH:27]

Participants

6

Reactant 4

HCID 962WaterHCID 15165112-Chloro-4-iodopyridineHCID 574499712-(2-Chloro-5-methoxy-phenyl)-propionaldehydeHCID 178461733HCID 178461733, compound

Product 1

HCID 866291052-(2-Chloro-5-methoxy-phenyl)-1-(2-chloro-pyridin-4-yl)-propan-1-olYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-Chloro-4-iodopyridine (1.03 g, [CAS Reg. No. 153034-86-7]) was dissolved in THF (50 mL) and a solution of isopropylmagnesiumchloride-lithium chloride complex (14% in THF, 3.13 mL) was added over a period of 3 minutes at r.t. The mixture was cooled in an ice bath and 2-(2-chloro-5-methoxy-phenyl)-propionaldehyde (710 mg) dissolved in THF (20 mL) was added dropwise over a period of 10 minutes. Stirring was continued for 1.5 hours. The reaction mixture was poured into water, extracted with ethyl acetate and the organic layer was washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane) to give the desired compound as a yellow oil (734 mg, 66%). MS (m/e)=312.0 [MH+].

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. additionwas added dropwise over a period of 10 minutes
  3. extractionextracted with ethyl acetate
  4. washthe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane)

Sources & evidence

ORD record
ord-a2d88496252849209412330103bd8679
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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