Dimethyl 5-aminoisophthalate → 5-[2-(4-Adamantan-1-yl-phenoxy)-acetylamino]-isophthalic acid dimethyl ester

HRID 1945373Notes

Reaction equation

HRID 1945373 reaction equation
[C:1]12([C:11]3[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17](O)=[O:18])=[CH:13][CH:12]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH3:22][O:23][C:24](=[O:36])[C:25]1[CH:34]=[C:33]([NH2:35])[CH:32]=[C:27]([C:28]([O:30][CH3:31])=[O:29])[CH:26]=1.Cl.C(N=C=N)C.ON1C2C=CC=CC=2N=N1>CN(C=O)C>[CH3:31][O:30][C:28](=[O:29])[C:27]1[CH:32]=[C:33]([NH:35][C:17](=[O:18])[CH2:16][O:15][C:14]2[CH:13]=[CH:12][C:11]([C:1]34[CH2:10][CH:5]5[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]5)[CH2:8]3)[CH2:2]4)=[CH:21][CH:20]=2)[CH:34]=[C:25]([C:24]([O:23][CH3:22])=[O:36])[CH:26]=1

Participants

6

Reactant 4

HCID 66831Dimethyl 5-aminoisophthalateHCID 757711-HydroxybenzotriazoleHCID 625381PMID26882240-Compound-8HCID 21883477Ethylcarbodiimide hydrochloride

Product 1

HCID 248110005-[2-(4-Adamantan-1-yl-phenoxy)-acetylamino]-isophthalic acid dimethyl esterYield 81.92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (4-adamantan-1-yl-phenoxy)-acetic acid (143.2 mg, 0.50 mmol), 5-aminoisophthalic acid dimethyl ester (156.9 mg, 0.75 mmol), N-3-dimethylaminopropyl)-N′-ethyl carbodiimide HCl (EDC) (143.8 mg, 0.75 mmol) and 1-hydroxybenzotriazole (HOBt) (101.4 mg, 0.75 mmol) in DMF (5 mL) was added N,N-disopropylethylamine, redistilled (DIPEA) (0.13 mL, 0.75 mmol). The mixture was stirred overnight, and then partitioned between ethyl acetate and 10% HCl. The organic phase washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (n-Hexane:Ethyl acetate:MeOH=9:3:1) to give 5-[2-(4-Adamantan-1-yl-phenoxy)-acetylamino]-isophthalic acid dimethyl ester as a light yellow solid (195.6 mg, 81.92% yield).

Workup

  1. additionwas added N,N-disopropylethylamine
  2. distillationredistilled (DIPEA) (0.13 mL, 0.75 mmol)
  3. custompartitioned between ethyl acetate and 10% HCl
  4. washThe organic phase washed with brine
  5. dry with materialdried (MgSO4 anh)
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel flash column chromatography (n-Hexane:Ethyl acetate:MeOH=9:3:1)

Sources & evidence

ORD record
ord-ba9f868104124fd286c3376f956beb65
Source dataset
uspto-grants-2013_03
Patent number
US08394799B2

Reaction notes

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