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

HRID 1430189ノート

反応式

HRID 1430189 の反応式
[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]

参加物

9

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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 (1H, br s), 8.28 (1H, d, J=8.1 Hz), 7.53-7.57 (2H, m), 7.42-7.46 (2H, m), 7.27 (1H, dd, J=8.1, 1.6 Hz), 7.14 (1H, d, J=1.5 Hz), 4.29 (2H, d, J=4.8 Hz), 4.28 (2H, q, J=7.1 Hz), 4.09 (3H, s), 1.34 (3H, t, J=7.2 Hz). HPLC-MS: m/z 348 [M+H]+.

後処理

  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)

出典と根拠

ORDレコード
ord-8d1ed06579e44e62805f0d5272d47645
出典データセット
uspto-grants-2015_01
特許番号
US08940773B2

反応ノート

読み込み中…