Water → 5-Hydroxymethyl-2-(2-methylpropyl)thiazole

HRID 1783269Notes

Reaction equation

HRID 1783269 reaction equation
[C:1](=[S:7])([NH2:6])[CH2:2][CH:3]([CH3:5])[CH3:4].[CH:8]([CH:10](Cl)[C:11](OCC)=O)=[O:9].O.C(=O)(O)[O-].[Na+]>CN(C=O)C>[OH:9][CH2:8][C:10]1[S:7][C:1]([CH2:2][CH:3]([CH3:5])[CH3:4])=[N:6][CH:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 118030Ethyl (chloroformyl)acetateHCID 516892Sodium BicarbonateHCID 3034257Butanethioamide, 3-methyl-

Product 1

HCID 210859775-Hydroxymethyl-2-(2-methylpropyl)thiazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

Isovalerothioamide (6.0 g, 51 mmol) and ethyl formylchloroacetate (Heterocycles 32 (4), 693-701, (1991), 5.0 g, 33 mmol) are dissolved in dry DMF (20 mL), and heated to 95 degrees C. for 4 hours. The reaction is subsequently cooled to 0 degrees C., and cold water (50 mL) is added. The mixture is basified to pH=8 with solid sodium bicarbonate, then extracted with ether (3×35 mL). The combined organic extracts are washed with water, then saline and dried over magnesium sulfate, filtered, and concentrated. The residue is purified by flash chromatography (ethyl acetate/hexanes 4-10% elution) to give the desired product. NMR (CDCl3, 300 MHz) δ 8.27, 4.45-4.30, 3.70-3.50, 3.00-2.80, 2.30-2.10, 1.40-1.20, and 1.10-0.90.

Workup

  1. temperatureThe reaction is subsequently cooled to 0 degrees C
  2. extractionextracted with ether (3×35 mL)
  3. washThe combined organic extracts are washed with water
  4. dry with materialsaline and dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by flash chromatography (ethyl acetate/hexanes 4-10% elution)

Sources & evidence

ORD record
ord-8909ab9c1bbb4052a6f662c3ef28501b
Source dataset
uspto-grants-2009_03
Patent number
US07498436B2

Reaction notes

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