Diisopropylethylamine → (+/-)-3-({5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester

HRID 660983ノート

反応式

HRID 660983 の反応式
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:11]2[S:15][C:14]([C:16](O)=[O:17])=[CH:13][CH:12]=2)[CH3:10])[CH:5]=[C:4]([CH3:19])[C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1.Cl.[CH3:31][O:32][C:33](=[O:37])[CH2:34][CH2:35][NH2:36].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O>[CH3:31][O:32][C:33](=[O:37])[CH2:34][CH2:35][NH:36][C:16]([C:14]1[S:15][C:11]([CH:9]([O:8][C:6]2[CH:7]=[C:2]([CH3:1])[C:3]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][CH:21]=3)=[C:4]([CH3:19])[CH:5]=2)[CH3:10])=[CH:12][CH:13]=1)=[O:17]

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67485022(+/-)-5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carboxylic acid

生成物 1

HCID 59356032(+/-)-3-({5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester収率 75%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of (-±)-5-[1-(2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carboxylic acid (0.545 g, 1.30 mmol), 3-amino-propionic acid methyl ester hydrochloride (0.199 g, 1.43 mmol), and 1-hydroxybenzotriazole hydrate (HOBt, 0.217 g, 1.60 mmol) in DMF (13.0 mL) is added N,N-diisopropylethylamine (0.67 mL, 3.84 mmol), then N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI, 0.330 g, 1.72 mmol) and stirred overnight. The reaction mixture is poured into H2O (25 mL) and extracted with EtOAc (3×25 mL). Combined organic extracts are washed with H2O, brine, dried over MgSO4, filtered, and concentrated. The residue is loaded onto silica gel and eluted using hexanes with an ethyl acetate gradient from 0% to 75% to provide (±)-3-({5-[1-(2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester (0.490 g, 75%) as a white foam. MS (ES): 504.3 [M−H]−.

後処理

  1. extractionextracted with EtOAc (3×25 mL)
  2. washCombined organic extracts are washed with H2O, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted

出典と根拠

ORDレコード
ord-f1e48613793d4d68a32a3799c0173354
出典データセット
uspto-grants-2011_12
特許番号
US08084489B2

反応ノート

読み込み中…