Ethanolamine → 2-(2-o-Tolyl-chroman-6-yloxy)-thiazole-5-carboxylic acid (2-hydroxy-ethyl)-amide

HRID 1404207Notes

Reaction equation

HRID 1404207 reaction equation
[Li+].[C:2]1([CH3:27])[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][C:19]3[S:20][C:21]([C:24]([O-])=[O:25])=[CH:22][N:23]=3)[CH:14]=2)[O:9]1.CN(C)C=O.ON1C2C=CC=CC=2N=N1.C[N:44]1CC[O:47][CH2:46][CH2:45]1.C(CN)O>O>[OH:47][CH2:46][CH2:45][NH:44][C:24]([C:21]1[S:20][C:19]([O:18][C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[O:9][CH:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:27])[CH2:17][CH2:16]3)=[N:23][CH:22]=1)=[O:25]

Participants

7

Reactant 5

HCID 700EthanolamineHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 712929842-(2-o-Tolyl-chroman-6-yloxy)-thiazole-5-carboxylic acid lithium salt

Product 1

HCID 715094942-(2-o-Tolyl-chroman-6-yloxy)-thiazole-5-carboxylic acid (2-hydroxy-ethyl)-amide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 2-(2-o-tolyl-chroman-6-yloxy)-thiazole-5-carboxylic acid lithium salt (100 mg, 0.27 mmol) in dimethylformamide (2 ml) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72 mg, 0.38 mmol, 1.4 eq), 1-hydroxy-benzotriazole (51 mg, 0.38 mmol, 1.4 eq) and N-methylmorpholine (68 mg, 0.67 mmol, 2.5 eq) were added and the mixture was stirred at room temperature for 15 min. Ethanolamine (25 mg, 0.40 mmol, 1.5 eq) was added and stirring was continued for 16 h. The mixture was diluted with water and the aqueous layer extracted with ethyl acetate. The combined organic layers were washed with a diluted aqueous solution of sodium carbonate and brine, dried over sodium sulfate and filtered, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol gradient). The desired compound was obtained as a white powder (43 mg, 39%).

Workup

  1. stirringstirring
  2. waitwas continued for 16 h
  3. extractionthe aqueous layer extracted with ethyl acetate
  4. washThe combined organic layers were washed with a diluted aqueous solution of sodium carbonate and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customThe crude product was purified by column chromatography (silica gel, ethyl acetate/methanol gradient)

Sources & evidence

ORD record
ord-413319050c58480c941e0286e89a1c10
Source dataset
uspto-grants-2014_12
Patent number
US08912224B2

Reaction notes

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