1-Hydroxybenzotriazole → 2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-butyric acid methyl ester

HRID 1889264Notes

Reaction equation

HRID 1889264 reaction equation
[O:1]([CH2:8][CH2:9][O:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][C:12]=1[C:21](O)=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C.Cl.[CH3:56][O:57][C:58](=[O:64])[C:59]([NH2:63])([CH3:62])[CH2:60][CH3:61]>CN(C=O)C>[CH3:56][O:57][C:58](=[O:64])[C:59]([CH3:62])([NH:63][C:21]([C:12]1[CH:13]=[CH:14][C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]=1[O:10][CH2:9][CH2:8][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:22])[CH2:60][CH3:61]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 44828790Methyl 2-amino-2-methylbutanoate hydrochlorideHCID 688427781-(2-Phenoxy-ethoxy)-naphthalene-2-carboxylic acid

Product 1

HCID 688406072-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-butyric acid methyl esterYield 66.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 487 mg 1-(2-phenoxy-ethoxy)-naphthalene-2-carboxylic acid in 6 ml abs. DMF under inert atmosphere 216 mg 1-hydroxybenzotriazole, 306 mg 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 293 μl of N,N-diisopropylethylamine were added at 0° C. After 30 minutes at 0° C. 252 mg of 2-amino-2-methyl-butyric acid methyl ester hydrochloride, followed by 293 μl of N,N-diisopropylethylamine were added. After 16 h at room temperature the reaction mixture was concentrated, the residue was taken up in ethyl acetate and washed with 2 M HCl, aqueous sodium carbonate solution (10%) and brine. The organic layer was dried over magnesium sulphate and concentrated. The resulting residue was purified by chromatography on silica (ethyl acetate/heptane) to yield 419 mg of 2-methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-butyric acid methyl ester.

Workup

  1. additionwere added
  2. concentrationAfter 16 h at room temperature the reaction mixture was concentrated
  3. washwashed with 2 M HCl, aqueous sodium carbonate solution (10%) and brine
  4. dry with materialThe organic layer was dried over magnesium sulphate
  5. concentrationconcentrated
  6. customThe resulting residue was purified by chromatography on silica (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-1c17c27599744442aa0c233bf7e8692e
Source dataset
uspto-grants-2013_08
Patent number
US08501981B2

Reaction notes

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