Sodium Chloride → 3-oxo-2-(4-pyrazol-1-ylbenzyl)thiobutyric acid S-tert-butyl ester

HRID 1944304Notes

Reaction equation

HRID 1944304 reaction equation
[C:1]([S:5][C:6](=[O:11])[CH2:7][C:8](=[O:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH:26]=[CH:25][CH:24]=[N:23]2)=[CH:18][CH:17]=1.[Cl-].[Na+]>COCCOC.C(O)(=O)C.O>[C:1]([S:5][C:6](=[O:11])[CH:7]([CH2:15][C:16]1[CH:17]=[CH:18][C:19]([N:22]2[CH:26]=[CH:25][CH:24]=[N:23]2)=[CH:20][CH:21]=1)[C:8](=[O:10])[CH3:9])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 140007Butanethioic acid, 3-oxo-, S-(1,1-dimethylethyl) esterHCID 27764791-[4-(Bromomethyl)Phenyl]-1H-Pyrazole

Product 1

HCID 866423723-oxo-2-(4-pyrazol-1-ylbenzyl)thiobutyric acid S-tert-butyl esterYield 8.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
15 °C

Procedure

A solution of 3-oxothiobutyric acid S-tert-butyl ester (3.7 g) in 1,2-dimethoxyethane (5.0 mL) was added to a stirred suspension of sodium hydride (60% in oil, 0.92 g) in 1,2-dimethoxyethane (25 mL) at −10° C., and the resulting mixture was warmed to 15° C. over 15 minutes, cooled to −10° C. and then treated dropwise with a mixture of 1-(4-bromomethylphenyl)-1H-pyrazole (5.0 g) in 1,2-dimethoxyethane (20 mL) over a period of 30 minutes. The resulting mixture was warmed to room temperature and then stirred at this temperature for overnight. The mixture was diluted water, pH adjusted to 5 by the addition of glacial acetic acid and then saturated with sodium chloride. The mixture was extracted ethyl acetate and the combined extracts were dried over magnesium sulfate and then concentrated under reduced pressure. Purification of the residue purified by column chromatography on silica gel, eluting with a mixture of pentane, dichloromethane and ethyl acetate (1:3:0, 0:1:0 to 0:10:1 by volume) gave title compound as a colourless gum (0.6 g).

Workup

  1. temperaturecooled to −10° C.
  2. temperatureThe resulting mixture was warmed to room temperature
  3. extractionThe mixture was extracted ethyl acetate
  4. dry with materialthe combined extracts were dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue
  7. custompurified by column chromatography on silica gel
  8. washeluting with a mixture of pentane, dichloromethane and ethyl acetate (1:3:0, 0:1:0 to 0:10:1 by volume)

Sources & evidence

ORD record
ord-9b1d23ab49724ba58f89fee51da8e88e
Source dataset
uspto-grants-2013_03
Patent number
US08394830B2

Reaction notes

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