Sodium hydride → tert-Butyl 2-(diethoxyphosphoryl)-3-(1,3-thiazol-4-yl)propanoate

HRID 1179284Notes

Reaction equation

HRID 1179284 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].[H-].[Na+].Br[CH2:20][C:21]1[N:22]=[CH:23][S:24][CH:25]=1>CN(C)C=O.C1(C)C=CC=CC=1>[CH2:7]([O:6][P:4]([CH:9]([CH2:20][C:21]1[N:22]=[CH:23][S:24][CH:25]=1)[C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])([O:3][CH2:1][CH3:2])=[O:5])[CH3:8]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 2773685tert-Butyl diethylphosphonoacetateHCID 98989844-(Bromomethyl)thiazole

Product 1

HCID 86602109tert-Butyl 2-(diethoxyphosphoryl)-3-(1,3-thiazol-4-yl)propanoateYield 35%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl diethylphosphonoacetate (15.6 g, 62 mmol) in dimethylformamide (50 mL) was added sodiumhydride (60% dispersion in mineral oil, 2.48 g, 62 mmol) at 0° C. under nitrogen atmosphere. After 45 min, to the mixture was added a solution of 4-(bromomethyl)-1,3-thiazole in toluene (27 g). The mixture was stirred at room temperature overnight. The mixture was quenched with water and extracted with toluene/ethyl acetate (1/3). The combined organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (1/2 to 100% ethyl acetate) to afford 7.17 g (35%) of the title compound as a colorless oil:

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with toluene/ethyl acetate (1/3)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (1/2 to 100% ethyl acetate)

Sources & evidence

ORD record
ord-4940483e1c9e4befb44ad7c92cd8f09e
Source dataset
uspto-grants-2007_10
Patent number
US07279486B2

Reaction notes

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