Iodine → (R)-2-[3-(3-Methoxypropoxy)-4-methoxybenzyl]-3-methylbutan-1-OL

HRID 744834Notes

Reaction equation

HRID 744834 reaction equation
[CH:1]([C@@H:4]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH2:18][CH2:19][CH2:20][O:21][CH3:22])[CH:10]=1)[C:5](O)=[O:6])([CH3:3])[CH3:2].[BH4-].[Na+].II.CO>O1CCCC1>[CH:1]([C@@H:4]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH2:18][CH2:19][CH2:20][O:21][CH3:22])[CH:10]=1)[CH2:5][OH:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 807IodineHCID 887MethanolHCID 4311764Sodium borohydrideHCID 9944529(2R)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutanoic acid

Product 1

HCID 9835828(R)-2-[3-(3-Methoxypropoxy)-4-methoxybenzyl]-3-methylbutan-1-OL

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

186 g of 2(R)-isopropyl-3-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-propionic acid in 0.5 liter of tetrahydrofuran are added dropwise at room temperature to a stirred mixture of 27.2 g of sodium borohydride in 1.5 liters of tetrahydrofuran. After 45 minutes a solution of 76.2 g of iodine in 1 liter of tetrahydrofuran is added dropwise. The reaction mixture is stirred for 4 days and then 1 liter of methanol is carefully added dropwise. After evaporation of the solvent the residue is taken up in 2 liters of 2N hydrochloric acid and extracted repeatedly with ethyl acetate. The organic extracts are washed in succession with water, saturated sodium thiosulfate solution, water/saturated sodium chloride solution (1:1), 0.1N sodium hydroxide solution and saturated sodium chloride solution. The organic extracts are concentrated by evaporation and purified by FC (2.4 kg of silica gel, ethyl acetate/hexane=1:4). The title compound is obtained: Rf (ethyl acetate/hexane=1:1)=0.28.

Workup

  1. customAfter evaporation of the solvent the residue
  2. extractionextracted repeatedly with ethyl acetate
  3. washThe organic extracts are washed in succession with water, saturated sodium thiosulfate solution, water/saturated sodium chloride solution (1:1), 0.1N sodium hydroxide solution and saturated sodium chloride solution
  4. concentrationThe organic extracts are concentrated by evaporation
  5. custompurified by FC (2.4 kg of silica gel, ethyl acetate/hexane=1:4)

Sources & evidence

ORD record
ord-8398170268cd44e98083d6f9754e3ba7
Source dataset
uspto-grants-1996_09
Patent number
US05559111

Reaction notes

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