Ethanolamine → N-[(S)-2-t-butoxy-1-(2-hydroxyethylcarbamoyl)ethyl]-4-methoxy-3-[(E)-2-(4-trifluoromethoxyphenyl)vinyl]-benzamide

HRID 558432Notes

Reaction equation

HRID 558432 reaction equation
[C:1]([O:5][CH2:6][C@H:7]([NH:11][C:12](=[O:34])[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15](/[CH:21]=[CH:22]/[C:23]2[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=2)[CH:14]=1)[C:8](O)=[O:9])([CH3:4])([CH3:3])[CH3:2].[OH:35][CH2:36][CH2:37][NH2:38].O.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:1]([O:5][CH2:6][C@H:7]([NH:11][C:12](=[O:34])[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15](/[CH:21]=[CH:22]/[C:23]2[CH:24]=[CH:25][C:26]([O:29][C:30]([F:31])([F:32])[F:33])=[CH:27][CH:28]=2)[CH:14]=1)[C:8](=[O:9])[NH:38][CH2:37][CH2:36][OH:35])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 700Ethanolamine2×HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrate2×HCID 67002188(S)-3-t-butoxy-2-{4-methoxy-3-[(E)-2-(4-trifluoromethoxyphenyl)vinyl]benzoylamino}propionic acid

Product 1

HCID 67001634N-[(S)-2-t-butoxy-1-(2-hydroxyethylcarbamoyl)ethyl]-4-methoxy-3-[(E)-2-(4-trifluoromethoxyphenyl)vinyl]-benzamideYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-3-t-butoxy-2-{4-methoxy-3-[(E)-2-(4-trifluoromethoxyphenyl)vinyl]benzoylamino}propionic acid (25 mg), 2-hydroxyethylamine (9 μL), benzotriazol-1-ol monohydrate (19 mg), and (3-dimethylaminopropyl)-ethylcarbodiimide hydrochloride (25 mg) were dissolved in 2 mL of N,N-dimethylformamide, and then, N,N-diisopropylethyl-amine (53 μL) was added to the solution. The solution was stirred overnight at room temperature. Then, 2-hydroxyethylamine (9 μL), benzotriazol-1-ol monohydrate (19 mg), and (3-dimethylaminopropyl)-ethylcarbodiimide hydrochloride (25 mg) were added again to the solution, and the solution was further stirred overnight. After removal of the solvent under reduced pressure, to the obtained residue was added water, and the mixture was extracted three times with dichloromethane. The respective organic layers were combined, whereafter the combined organic layer was washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The anhydrous sodium sulfate was separated by filtration, and washed with dichloromethane. The filtrate and the washings were combined, and dichloromethane was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 44 mg (76%) of N—[(S)-2-t-butoxy-1-(2-hydroxyethylcarbamoyl)ethyl]-4-methoxy-3-[(E)-2-(4-trifluoromethoxyphenyl)vinyl]-benzamide.

Workup

  1. waitthe solution was further stirred overnight
  2. customAfter removal of the solvent under reduced pressure
  3. additionto the obtained residue was added water
  4. extractionthe mixture was extracted three times with dichloromethane
  5. washwas washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe anhydrous sodium sulfate was separated by filtration
  8. washwashed with dichloromethane
  9. distillationdichloromethane was distilled off under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-38bc381fba2c4f8c8a00556d35f4b17f
Source dataset
uspto-grants-2011_11
Patent number
US08063046B2

Reaction notes

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