Acetamidomalonic acid diethyl ester → Diethyl 2-acetylamino-2-(5-thiazolylmethyl)malonate

HRID 47759Notes

Reaction equation

HRID 47759 reaction equation
[Na].Cl[CH2:3][C:4]1[S:8][CH:7]=[N:6][CH:5]=1.[C:9]([NH:12][CH:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])(=[O:11])[CH3:10]>C(O)C>[C:9]([NH:12][C:13]([CH2:3][C:4]1[S:8][CH:7]=[N:6][CH:5]=1)([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])(=[O:11])[CH3:10]

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 2054815-(Chloromethyl)thiazoleHCID 5360545Sodium

Product 1

HCID 22747897Diethyl 2-acetylamino-2-(5-thiazolylmethyl)malonate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
75 °C

Procedure

after dissolving 1.24 g of sodium in 20 cm3 of ethanol, 10.86 cm3 of diethyl acetamidomalonate are added, followed by heating at a temperature in the region of 75° C. After 15 minutes, a solution of 5-chloromethylthiazole in 20 cm3 of ethanol is added, followed by heating for 2 hours at a temperature in the region of 75° C. The reaction medium is evaporated under reduced pressure (1 kPa) at a temperature in the region of 40° C. The residue is chromatographed under an argon pressure of 60 kPa on a column of silica gel (particle size 60-200μ; diameter 6.5 cm; height 40 cm), eluting with a dichloromethane/methanol mixture (99/1 by volume), a dichloromethane/methanol mixture (98/02 by volume) and then a dichloromethane/methanol mixture (95/5 by volume). The fractions containing the expected product are combined and then concentrated under the above conditions. 3.3 g of diethyl 2-acetylamino-2-(5-thiazolylmethyl)malonate are obtained in the form of an orange-colored solid [1H NMR spectrum (300 MHz, (CD3)2SO-d6, δ in ppm): 1.18 (t, J=7.5 Hz: 6H); 2.00 (s: 3H); 3.75 (s: 2H); 4.17 (q, J=7.5 Hz: 4H); 7.61 (s: 1H); 8.37 (broad s: 1H); 9.00 (s: 1H)].

Workup

  1. additionare added
  2. temperatureby heating for 2 hours at a temperature in the region of 75° C
  3. customThe reaction medium is evaporated under reduced pressure (1 kPa) at a temperature in the region of 40° C
  4. customThe residue is chromatographed under an argon pressure of 60 kPa on a column of silica gel (particle size 60-200μ; diameter 6.5 cm; height 40 cm)
  5. washeluting with a dichloromethane/methanol mixture (99/1 by volume)
  6. additionThe fractions containing the expected product
  7. concentrationconcentrated under the above conditions

Sources & evidence

ORD record
ord-006e1b277ce74603ac959a73c436c648
Source dataset
uspto-grants-2004_03
Patent number
US06699895B2

Reaction notes

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