1,8-Diazabicyclo(5.4.0)undec-7-ene → (S)-5-tert-butyl-oxazole-2-carboxylic acid (1-thiophen-2-yl-ethyl)-amide

HRID 1870087Notes

Reaction equation

HRID 1870087 reaction equation
C(C1NC=CN=1)(C1NC=CN=1)=O.[C:13]([C:17]1[O:21][C:20]([C:22]([OH:24])=O)=[N:19][CH:18]=1)([CH3:16])([CH3:15])[CH3:14].[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[C@@H:30]([NH2:32])[CH3:31].C1CCN2C(=NCCC2)CC1>C1COCC1>[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[C@@H:30]([NH:32][C:22]([C:20]1[O:21][C:17]([C:13]([CH3:14])([CH3:15])[CH3:16])=[CH:18][N:19]=1)=[O:24])[CH3:31]

Participants

6

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 6546851(1S)-1-(thiophen-2-yl)ethan-1-amineHCID 110302445-(tert-Butyl)oxazole-2-carboxylic acid

Product 1

HCID 11011326(S)-5-tert-butyl-oxazole-2-carboxylic acid (1-thiophen-2-yl-ethyl)-amideYield 63.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of carbonyl diimidazole (CDI) (2.42 g, 15 mmol) in THF (40 ml) is added to a stirred solution of 5-tert-butyl-oxazole-2-carboxylic acid (2.3 g, 13.6 mmol) in THF (40 ml). The mixture is stirred for 30 min, then (S)-(1-thiophen-2-yl-ethyl)-amine (2.59 g, 20.4 mmol) is added, followed 10 min later by a solution of DBU (2.24 ml, 15 mmol) in THF (20 ml). The mixture is refluxed for 16 h and the THF is then removed by distillation. The residue is dissolved in ethyl acetate and the organic solution is washed with 2N hydrochloric acid and then twice with water. The organic phase is dried over sodium sulfate and evaporated in vacuo. The residue is purified by flash column chromatography (silica gel, petroleum ether/ethyl acetate 7:3 v/v) to give (S)-5-tert-butyl-oxazole-2-carboxylic acid (1-thiophen-2-yl-ethyl)-amide (2.40 g, 63%) as an oil.

Workup

  1. temperatureThe mixture is refluxed for 16 h
  2. customthe THF is then removed by distillation
  3. dissolutionThe residue is dissolved in ethyl acetate
  4. washthe organic solution is washed with 2N hydrochloric acid
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. customevaporated in vacuo
  7. customThe residue is purified by flash column chromatography (silica gel, petroleum ether/ethyl acetate 7:3 v/v)

Sources & evidence

ORD record
ord-28d3a24fc3514b0c880225d10fdbe871
Source dataset
uspto-grants-2000_08
Patent number
US06096688

Reaction notes

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