Chlorotrimethylsilane → 3-(2,3-Dimethoxy-pyridin-4-yl)-3-hydroxy-pentanoic acid tert-butyl ester

HRID 2246191Notes

Reaction equation

HRID 2246191 reaction equation
C[Si](Cl)(C)C.[C:6]([O:10][C:11](=[O:14])[CH2:12]Br)([CH3:9])([CH3:8])[CH3:7].[CH3:15][O:16][C:17]1[C:22]([O:23][CH3:24])=[C:21]([C:25](=[O:28])[CH2:26][CH3:27])[CH:20]=[CH:19][N:18]=1>C(OCC)C.O1CCCC1.[Zn]>[C:6]([O:10][C:11](=[O:14])[CH2:12][C:25]([C:21]1[CH:20]=[CH:19][N:18]=[C:17]([O:16][CH3:15])[C:22]=1[O:23][CH3:24])([OH:28])[CH2:26][CH3:27])([CH3:9])([CH3:8])[CH3:7]

Participants

7

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 79177tert-Butyl bromoacetateHCID 592179421-(2,3-Dimethoxy-pyridin-4-yl)-propan-1-one

Product 1

HCID 592179313-(2,3-Dimethoxy-pyridin-4-yl)-3-hydroxy-pentanoic acid tert-butyl esterYield 72.6%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of zinc (23.1 g; 353.9 mmol) in anhydrous diethyl ether (400 mL) was added trimethylsilyl chloride (0.5 mL). The mixture was stirred for 15 minutes at room temperature and refluxed. Bromoacetic acid tert-butyl ester (56.5 g, 290.0 mmol) was added dropwise and the reaction continued refluxing for an additional 1 hour. The mixture was then cooled to room temperature and cannulated to a solution of 1-(2,3-dimethoxy-pyridin-4-yl)-propan-1-one (13.8 g; 70.8 mmol) in anhydrous tetrahydrofuran (300 mL). The reaction was stirred for 16 hours at room temperature and quenched with saturated ammonium chloride solution. The aqueous layer was extracted with dichloromethane. The combined extracts were dried over sodium sulfate and concentrated under reduced pressure and purified by chromatography (SiO2; 2-10% ethyl acetate/hexane) to give the product 3-(2,3-dimethoxy-pyridin-4-yl)-3-hydroxy-pentanoic acid tert-butyl ester (6) (16.0 g).

Workup

  1. temperaturerefluxed
  2. temperaturethe reaction continued refluxing for an additional 1 hour
  3. temperatureThe mixture was then cooled to room temperature
  4. stirringThe reaction was stirred for 16 hours at room temperature
  5. customquenched with saturated ammonium chloride solution
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. dry with materialThe combined extracts were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. custompurified by chromatography (SiO2; 2-10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-09cf9b94fdbd460a9094f305a8b1eadc
Source dataset
uspto-grants-2010_03
Patent number
US07687487B2

Reaction notes

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