Potassium Iodide → Methyl 2-(4-(3-(tert-butyldimethylsilyloxy)propoxy)-2-methoxybenzyl)-3-oxobutanoate

HRID 2207083Notes

Reaction equation

HRID 2207083 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].[C:11]([Si:15]([O:18][CH2:19][CH2:20][CH2:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29]Cl)=[C:25]([O:31][CH3:32])[CH:24]=1)([CH3:17])[CH3:16])([CH3:14])([CH3:13])[CH3:12].[I-].[K+]>CN(C=O)C.O>[Si:15]([O:18][CH2:19][CH2:20][CH2:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH:2]([C:3](=[O:4])[CH3:5])[C:1]([O:7][CH3:8])=[O:6])=[C:25]([O:31][CH3:32])[CH:24]=1)([C:11]([CH3:13])([CH3:12])[CH3:14])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 123781615Tert-butyl {3-[4-(chloromethyl)-3-methoxyphenoxy]propoxy}dimethylsilane

Product 1

HCID 68752908Methyl 2-(4-(3-(tert-butyldimethylsilyloxy)propoxy)-2-methoxybenzyl)-3-oxobutanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

Methyl acetoacetate (4.18 mL) was added to a suspension of NaH (55% oil dispersion, 1.70 g) in DMF (60 mL) at 0° C. and stirred at r.t. for 0.5 h. The product from step (iii) (10.0 g) in DMF (60 mL) and potassium iodide (4.73 g) were added to the mixture and stirred at 80° C. for 6 h. The mixture was cooled to RT and diluted with water and extracted with EtOAc. And the combined organic solutions were washed with water and brine, dried and concentrated. The residue was purified by silica gel chromatography to give 9.98 g of the subtitle compound as a yellow oil; 1H NMR: 6.99 (1H, d), 6.42 (1H, d), 6.37 (1H, dd), 4.02 (2H, t), 3.89 (1H, t), 3.80 (3H, s), 3.79 (2H, t), 3.67 (3H, s), 2.99-3.14 (2H, m), 2.17 (3H, s), 1.92-2.00 (2H, m), 0.88 (9H, s), 0.04 (6H, s).

Workup

  1. stirringstirred at 80° C. for 6 h
  2. temperatureThe mixture was cooled to RT
  3. extractionextracted with EtOAc
  4. washAnd the combined organic solutions were washed with water and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ee5d7cc014a940c09a52001631c54ab1
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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