Ethyl isocyanoacetate → HCID 64269051, compound

HRID 2244391Notes

Reaction equation

HRID 2244391 reaction equation
CC([O-])(C)C.[K+].[CH2:7]([O:9][C:10](=[O:14])[CH2:11][N+:12]#[C-:13])[CH3:8].[N:15]([C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1)=[C:16]=[S:17]>O1CCCC1>[CH2:7]([O:9][C:10]([C:11]1[N:12]=[CH:13][S:17][C:16]=1[NH:15][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1)=[O:14])[CH3:8]

Participants

5

Reactant 3

HCID 533707Ethyl isocyanoacetateHCID 27372423-Pyridyl isothiocyanateHCID 23665647Potassium tert-butoxide

Product 1

HCID 64269051HCID 64269051, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

A three-necked flask equipped with a mechanical stirrer, a dropping funnel and an argon inlet was charged with anhydrous tetrahydrofurane (THF) (25.00 ml). Solid potassium tert-butylate (5.46 g, 44.20 mmol) was added and the slurry was stirred until dissolution was complete. The mixture was cooled to −40° C. by means of a dry ice/acetone bath. A solution of isocyano-acetic acid ethyl ester (5.00 g, 44.20 mmol) and 3-isothiocyanato-pyridine (6.02 g, 44.20 mmol) in anhydrous THF (50.00 ml) was added dropwise via the dropping funnel at such a rate that the temperature did not exceed −35° C. and the mixture remained homogeneously stirred (a thick precipitate forms). After addition was complete, the mixture was stirred for further 1 hour letting the temperature free to rise. The reaction was quenched by addition of glacial acetic acid (2.50 ml). The mixture was diluted with THF and ethyl acetate and filtered through celite. The filtrate was evaporated to a dark yellow solid residue, which was purified by flash chromatography (heptane/ethyl acetate) to yield 5-(pyridin-3-ylamino)-thiazole-4-carboxylic acid ethyl ester (4.85 g, 44%) as a light yellow solid, MS (ISP): m/e=250.2 (M+H+).

Workup

  1. customA three-necked flask equipped with a mechanical stirrer, a dropping funnel and an argon inlet
  2. customdid not exceed −35° C.
  3. stirringthe mixture remained homogeneously stirred (a thick precipitate forms)
  4. additionAfter addition
  5. stirringthe mixture was stirred for further 1 hour
  6. customThe reaction was quenched by addition of glacial acetic acid (2.50 ml)
  7. additionThe mixture was diluted with THF and ethyl acetate
  8. filtrationfiltered through celite
  9. customThe filtrate was evaporated to a dark yellow solid residue, which
  10. customwas purified by flash chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-c5ca69664bae4dbcb5d84de36c6f7170
Source dataset
uspto-grants-2010_03
Patent number
US07678815B2

Reaction notes

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