Sodium hydride → Diethyl 2-(tert-butoxyformamido)-2-[(5-oxazolyl)methyl]malonate

HRID 635641

Reaction equation

HRID 635641 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][CH:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[CH2:23][C:24]1[O:28][CH:27]=[N:26][CH:25]=1>C(O)C>[C:3]([O:7][C:8]([NH:10][C:11]([CH2:23][C:24]1[O:28][CH:27]=[N:26][CH:25]=1)([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 382219Diethyl 2-((tert-butoxycarbonyl)amino)malonateHCID 152908805-(Chloromethyl)-1,3-oxazole

Product 1

HCID 70092767Diethyl 2-(tert-butoxyformamido)-2-[(5-oxazolyl)methyl]malonate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

301 mg of a 60% dispersion of sodium hydride in mineral oil were added portionwise to 60 ml of anhydrous ethanol at 0° C. and the resulting suspension was stirred at 0° C. for 5 minutes. 1.88 g of diethyl 2-(tert-butoxyformamido)malonate were added and the mixture was warmed to room temperature. After stirring at room temperature for 10 minutes 805 mg of 5-(chloromethyl)oxazole were added. The mixture was stirred at room temperature for 30 minutes and at 60° C. for 1 hour. The solvent was evaporated and the crude product was dissolved in diethyl ether and washed with water. Sodium chloride was added to the aqueous layer, which was then extracted with diethyl ether. The combined organic layers were dried over magnesium sulphate and the solvent was removed by evaporation. Purification of the residue by chromatography on silica gel using ethyl acetate/hexane (1:2) for the elution gave diethyl 2-(tert-butoxyformamido)-2-[(5-oxazolyl)methyl]malonate, 1H NMR (250 MHz, CDCl3) δ: 1.3 (t,6H), 1.45 (s,9H), 3.75 (s,2H), 4.2 (m,4H), 5.85 (s,1H), 6.8 (s,1H), 7.75 (s,1H).

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. additionwere added
  3. stirringThe mixture was stirred at room temperature for 30 minutes and at 60° C. for 1 hour
  4. customThe solvent was evaporated
  5. dissolutionthe crude product was dissolved in diethyl ether
  6. washwashed with water
  7. additionSodium chloride was added to the aqueous layer, which
  8. extractionwas then extracted with diethyl ether
  9. dry with materialThe combined organic layers were dried over magnesium sulphate
  10. customthe solvent was removed by evaporation
  11. customPurification of the residue by chromatography on silica gel
  12. washfor the elution

Sources & evidence

ORD record
ord-f05699401b8847e68994ecec9e2d6bc7
Source dataset
uspto-grants-2001_02
Patent number
US06187905B1

Linked notes

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