Diisopropylcarbodiimide → (S)-methyl 2-(2-(3,5-dimethylphenyl)acetamido)-3-(1H-indol-3-yl)propanoate

HRID 71025

Reaction equation

HRID 71025 reaction equation
CC(N=C=NC(C)C)C.[CH3:10][O:11][C:12](=[O:25])[C@H:13]([CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][CH:17]=1)[NH2:14].[CH3:26][C:27]1[CH:28]=[C:29]([CH2:34][C:35](O)=[O:36])[CH:30]=[C:31]([CH3:33])[CH:32]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:26][C:27]1[CH:28]=[C:29]([CH2:34][C:35]([NH:14][C@@H:13]([CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[C:12]([O:11][CH3:10])=[O:25])=[O:36])[CH:30]=[C:31]([CH3:33])[CH:32]=1

Participants

6

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 77980L-Tryptophan, methyl esterHCID 47494952-(3,5-Dimethylphenyl)acetic acid

Product 1

HCID 67042226(S)-methyl 2-(2-(3,5-dimethylphenyl)acetamido)-3-(1H-indol-3-yl)propanoate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

DMAP (122.2 mg, 0.5 mmol) and DIC (N,N-diisopropylcarbodiimide) (235 μl, 1.5 mmol) were added to a solution of tryptophan methyl ester (255 mg, 1.0 mmol) and 3,5-dimethylphenylacetic acid (164 mg, 1.0 mmol) in dry DCM (11 ml). After 17 h at room temperature the solvent was removed under reduced pressure and the crude product was purified by flash chromatography (DCM containing 1% EtOH) to afford (S)-methyl 2-(2-(3,5-dimethylphenyl)acetamido)-3-(1H-indol-3-yl)propanoate. An aqueous solution of LiOH (1N, 4.5 ml, 4.5 mmol) was added to a solution of (S)-methyl 2-(2-(3,5-dimethylphenyl)acetamido)-3-(1H-indol-3-yl)propanoate (365 mg, 1 mmol) in methanol (24.5 ml) and the reaction mixture was stirred at room temperature for 4.5 h. Then water was added and methanol was removed under reduced pressure. The aqueous residue was washed with DCM (5×20 ml), treated with HCl 2N to obtain a pH 4 and extracted with DCM (3×25 ml). The organic phases were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure to afford (S)-2-(2-(3,5-dimethylphenyl)acetamido)-3-(1H-indol-3-yl)propionic acid (93% c.y.).

Workup

  1. customAfter 17 h at room temperature the solvent was removed under reduced pressure
  2. customthe crude product was purified by flash chromatography (DCM containing 1% EtOH)

Sources & evidence

ORD record
ord-910acda96cbd40a7b0df098feb9d2f80
Source dataset
uspto-grants-2014_09
Patent number
US08822698B2

Linked notes

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