Diisopropylethylamine → 2-[(4-Hydroxy-benzo[b]thiophene-5-carbonyl)-amino]-2-methyl-propionic acid tert-butyl ester

HRID 874746Notes

Reaction equation

HRID 874746 reaction equation
[OH:1][C:2]1[C:10]2[CH:9]=[CH:8][S:7][C:6]=2[CH:5]=[CH:4][C:3]=1[C:11]([OH:13])=O.Cl.[C:15]([O:19][C:20](=[O:25])[C:21]([NH2:24])([CH3:23])[CH3:22])([CH3:18])([CH3:17])[CH3:16].C(N(C(C)C)C(C)C)C.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(OCC)(=O)C>[C:15]([O:19][C:20](=[O:25])[C:21]([NH:24][C:11]([C:3]1[CH:4]=[CH:5][C:6]2[S:7][CH:8]=[CH:9][C:10]=2[C:2]=1[OH:1])=[O:13])([CH3:23])[CH3:22])([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 12186776Tert-butyl 2-amino-2-methylpropanoate hydrochlorideHCID 688459314-Hydroxybenzo[b]thiophene-5-carboxylic acid

Product 1

HCID 688411722-[(4-Hydroxy-benzo[b]thiophene-5-carbonyl)-amino]-2-methyl-propionic acid tert-butyl esterYield 64.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 300 mg 4-Hydroxy-benzo[b]thiophene-5-carboxylic acid in 5 ml N,N-dimethylformamide were added 42 mg 1-hydroxy-benzotriaziole and 285 mg 2-amino-2-methyl-propionic acid tert-butyl ester hydrochloride. At 0° C. 0.77 ml (600 mg) ethyl-diisopropyl-amine and 444 mg (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride were added. After 16 h at room temperature 0.51 ml (400 mg) ethyl-diisopropyl-amine and 444 mg (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride were added, and after additional 16 h the reaction was diluted with ethyl acetate and washed with brine. The organic layer was dried over magnesium sulphate and concentrated. The resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate) to afford 315 mg 2-[(4-hydroxy-benzo[b]thiophene-5-carbonyl)-amino]-2-methyl-propionic acid tert-butyl ester.

Workup

  1. customAt 0° C
  2. washwashed with brine
  3. dry with materialThe organic layer was dried over magnesium sulphate
  4. concentrationconcentrated
  5. customThe resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate)

Sources & evidence

ORD record
ord-5173d4ac11924a4986c9423d802e81d5
Source dataset
uspto-grants-2015_03
Patent number
US08980938B2

Reaction notes

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