Triethylamine → Ethyl 6-chloro-7-(4-(4-chloro-2-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1048183ノート

反応式

HRID 1048183 の反応式
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH2:11])=[C:5]([O:12][CH3:13])[CH:4]=1.C(N(CC)CC)C.[Cl:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][CH:34]=1)[O:28][CH2:27][CH2:26][CH:25]2[C:42]([O:44][CH2:45][CH3:46])=[O:43].O.N1(O)C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CCOC(C)=O>[Cl:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](=[O:38])[NH:11][CH2:10][CH2:9][C:6]3[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][C:5]=3[O:12][CH3:13])=[CH:35][CH:34]=1)[O:28][CH2:27][CH2:26][CH:25]2[C:42]([O:44][CH2:45][CH3:46])=[O:43]

参加物

8

反応物 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 670810862-(4-Chloro-2-methoxyphenyl)ethanamine hydrochloride

生成物 1

HCID 67080996Ethyl 6-chloro-7-(4-(4-chloro-2-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a suspension of 2-(4-chloro-2-methoxyphenyl)ethanamine hydrochloride (Preparation 8; 23.4 g, 105 mmol) in DCM (200 ml) was added triethylamine (16.8 ml, 120 mmol), and the mixture was allowed to stir for 30 minutes (solids did not go into solution). To this was added sequentially 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1; 37.8 g, 100 mmol, 1H-benzo[d][1,2,3]triazol-1-ol hydrate (15.4 g, 100 mmol), and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (23.1 g, 120 mmol), and the reaction was allowed to stir overnight (all solids went into solution after 2 hours). The reaction was diluted with EtOAc (600 ml) and washed with 600 mL portions of 1M HCl, saturated aqueous bicarbonate, and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was taken up in hot ethyl acetate (500 ml) and was crystallized by the addition of hexanes (1.5 L) to yield ethyl 6-chloro-7-(4-(4-chloro-2-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate (51.1 g, 93.9 mmol).

後処理

  1. customPreparation 1
  2. stirringto stir overnight (all solids went into solution after 2 hours)
  3. washwashed with 600 mL portions of 1M HCl, saturated aqueous bicarbonate, and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customwas crystallized by the addition of hexanes (1.5 L)

出典と根拠

ORDレコード
ord-0171e1f1b196484f80d3fc0f455d892e
出典データセット
uspto-grants-2013_10
特許番号
US08569522B2

反応ノート

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