1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [(4'-Chloro-3-methoxy-biphenyl-4-carbonyl)-amino]-acetic acid ethyl ester

HRID 1797995Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1797995
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[C:10]([O:17][CH3:18])[CH:9]=2)=[CH:4][CH:3]=1.Cl.[CH2:20]([O:22][C:23](=[O:26])[CH2:24][NH2:25])[CH3:21].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CCOC(C)=O.CN(C=O)C>[CH2:20]([O:22][C:23](=[O:26])[CH2:24][NH:25][C:14]([C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[CH:9][C:10]=1[O:17][CH3:18])=[O:16])[CH3:21]

Komponenten

9

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2723640Glycine ethyl ester, hydrochlorideHCID 248911994-(4-Chlorophenyl)-2-methoxybenzoic acid

Produkt 1

HCID 24891040[(4'-Chloro-3-methoxy-biphenyl-4-carbonyl)-amino]-acetic acid ethyl esterAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 4′-chloro-3-methoxy-biphenyl-4-carboxylic acid, 9, (0.325 g, 1.24 mmol) in CH2Cl2 (5 mL) and DMF (1.5 mL) at room temperature under N2 is added glycine ethyl ester hydrochloride (0.19 g, 1.36 mmol), 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide (EDCI) (0.261 g, 1.36 mmol), 1-hydroxybenzotriazole (HOBt) (0.033 g, 0.248 mmol) and diisopropylethylamine (DIPEA) (0.432 ml, 2.28 mmol). The resulting suspension is stirred for 16 hours after which the reaction mixture is diluted with EtOAc and washed with 1M HCl, 1M NaOH and saturated aqueous NaCl. The organic phase is separated, dried (MgSO4), filtered and concentrated under reduced pressure. The crude material is purified over silica (hexanes:EtOAc 1:1) to afford 0.364 g (85% yield) of the desired product as a colorless solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.51 (1 H, br s), 8.28 (1 H, d, J=8.1 Hz), 7.53-7.57 (2 H, m), 7.42-7.46 (2 H, m), 7.27 (1 H, dd, J=8.1, 1.6 Hz), 7.14 (1 H, d, J=1.5 Hz), 4.29 (2 H, d, J=4.8 Hz), 4.28 (2 H, q, J=7.1 Hz), 4.09 (3 H, s), 1.34 (3 H, t, J=7.2 Hz). HPLC-MS: m/z 348 [M+H]+.

Aufarbeitung

  1. washwashed with 1M HCl, 1M NaOH and saturated aqueous NaCl
  2. customThe organic phase is separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material is purified over silica (hexanes:EtOAc 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-6306865695b14cf7b8e0f2900bfa4052
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08343952B2

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