Ethyl 3-aminobenzoate → 3-[2-(4-Adamantan-1-yl-phenoxy)-acetylamino]-benzoic acid ethyl ester

HRID 1945370Notes

Reaction equation

HRID 1945370 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.[CH2:22]([O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([NH2:32])[CH:27]=1)[CH3:23].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH2:22]([O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][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:27]=1)[CH3:23]

Participants

7

Reactant 5

HCID 11400Ethyl 3-aminobenzoateHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 625381PMID26882240-Compound-8HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 248108943-[2-(4-Adamantan-1-yl-phenoxy)-acetylamino]-benzoic acid ethyl esterYield 89.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of [4-(1-adamantyl)phenoxy]acetic acid (143.2 mg, 0.5 mmol), 3-aminobenzoic acid ethyl ester (123.9 mg, 0.5 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 (6 mL) was added N,N-diisopropylethylamine, redistilled (DIPEA) (97.0 mg, 0.13 mL, 0.75 mmol). The mixture wag stirred overnight, and then partitioned between ethyl acetate and 10% HCl. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (n-Hexane:Ethyl acetate:MeOH=6:3:1) to give 3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-benzoic acid ethyl ester as a white solid (194.4 mg, 89.7% yield).

Workup

  1. distillationredistilled (DIPEA) (97.0 mg, 0.13 mL, 0.75 mmol)
  2. custompartitioned between ethyl acetate and 10% HCl
  3. washThe organic phase was washed with brine
  4. dry with materialdried (MgSO4 anh)
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash column chromatography (n-Hexane:Ethyl acetate:MeOH=6:3:1)

Sources & evidence

ORD record
ord-fd6b237e901545e893a67bc1978ab111
Source dataset
uspto-grants-2013_03
Patent number
US08394799B2

Reaction notes

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