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

HRID 1048183노트

반응식

HRID 1048183 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-0171e1f1b196484f80d3fc0f455d892e
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569522B2

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