Hydrochloric Acid → 3-(4-{4-[2-Dimethylcarbamoyl-2-(toluene-4-sulfonylamino)-ethyl]-phenoxy}-phenyl)-propionic acid methyl ester

HRID 748996ノート

反応式

HRID 748996 の反応式
Cl.Cl.[CH3:3][O:4][C:5](=[O:29])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([NH2:28])[C:23](=[O:27])[N:24]([CH3:26])[CH3:25])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1.CCN(C(C)C)C(C)C.[C:39]1([CH3:49])[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=1>C(Cl)Cl.C(O)(=O)C.C(OCC)(=O)C>[CH3:3][O:4][C:5](=[O:29])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([C:23](=[O:27])[N:24]([CH3:25])[CH3:26])[NH:28][S:45]([C:42]3[CH:43]=[CH:44][C:39]([CH3:49])=[CH:40][CH:41]=3)(=[O:47])=[O:46])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 691134593-{4-[4-(2-Amino-2-dimethylcarbamoyl-ethyl)-phenoxy]-phenyl}-propionic acid methyl ester hydrochloric acid salt

生成物 1

HCID 691137573-(4-{4-[2-Dimethylcarbamoyl-2-(toluene-4-sulfonylamino)-ethyl]-phenoxy}-phenyl)-propionic acid methyl ester収率 56.1%

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
2.5 °C

実験手順

Hydrochloride compound 23 (1.5 g, 3.69 mmol) was dissolved in CH2Cl2 (50 mL) and cooled to 0-5° C. N,N′-Diisopropylethylamine (1.28 mL, 7.74 mmol) was added to the above solution followed by addition of p-toluenesulfonyl chloride (0.58 g, 3.06 mmol) in small portions. The reaction mixture was then warmed up to room temperature and stirred overnight. The solvent was removed under reduced pressure and the residual oil was taken up in EtOAc (75 mL). The organic layer was washed with 2.0 M HCl (1×10 mL), water (1×50 mL), and brine (2×50 mL). The resulting EtOAc layer was dried and concentrated under reduced pressure to yield oil. Flash chromatography (hexanes:ethyl acetate—3:2 containing 1% acetic acid) yielded the desired sulfonamide 24 (0.9 g, 47%). 1H NMR (400 MHz, DMSO-d6): 7.54 (d, J=8.4 Hz, 2H), 7.29 (d, J=8.0 Hz, 2H), 7.22 (d, J=8.8 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H), 6.82 (d, J=8.4 Hz, 2H), 4.39 (m, 1H), 3.58 (s, 3H), 2.72-2.92 (m, 4H), 2.69 (s, 3H), 2.57-2.64 (m, 4H), 2.47 (s, 3H), 2.35 (s, 3H).

後処理

  1. temperatureThe reaction mixture was then warmed up to room temperature
  2. customThe solvent was removed under reduced pressure
  3. washThe organic layer was washed with 2.0 M HCl (1×10 mL), water (1×50 mL), and brine (2×50 mL)
  4. dry with materialThe resulting EtOAc layer was dried
  5. concentrationconcentrated under reduced pressure
  6. customto yield oil

出典と根拠

ORDレコード
ord-9c6840aae85c45ea8bf1d34cf83be389
出典データセット
uspto-grants-2008_07
特許番号
US07399786B2

反応ノート

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