2-(2-Ethoxyphenoxy)ethylamine → Tamsulosin

HRID 1294093

反応式

HRID 1294093 の反応式
[CH2:1]([O:3][C:4]1[CH:13]=[CH:12][CH:11]=[CH:10][C:5]=1[O:6][CH2:7][CH2:8][NH2:9])[CH3:2].[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23](=O)[CH3:24])=[CH:18][C:17]=1[S:26]([NH2:29])(=[O:28])=[O:27].[H][H]>CO.[Pt]>[CH3:2][CH2:1][O:3][C:4]1[CH:13]=[CH:12][CH:11]=[CH:10][C:5]=1[O:6][CH2:7][CH2:8][NH:9][C@@H:23]([CH2:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][CH3:14])=[C:17]([S:26]([NH2:29])(=[O:28])=[O:27])[CH:18]=1)[CH3:24]

参加物

6

反応物 3

HCID 53030422-(2-Ethoxyphenoxy)ethylamineHCID 141797592-Methoxy-5-(2-oxopropyl)benzenesulfonamideHCID 178418361HCID 178418361、化合物

生成物 1

HCID 129211Tamsulosin

試薬・触媒・溶媒 2

HCID 23939Platinum触媒HCID 887Methanol溶媒2 回

実験手順

2-(o-Ethoxyphenoxy)ethylamine (45 gm) was dissolved in methanol (250 mL). To this 2-methoxy-5-(2-oxopropyl)-benzene sulfonamide (55 gm), catalyst 5% platinum on carbon (12.1 gm) and methanol (330 mL) were added. The mixture was hydrogenated in autocalve at 55° C. at hydrogen pressure of 13 kg/cm2 for 5 hrs. The reaction mixture was cooled and the catalyst was filtered off. To the filtrate containing racemic tamsulosin, oxalic acid (14.3 gm) was added and the solvent was distilled off. To the residue, acetone (700 mL) was added and stirred at reflux temperature for 30 mins. The mixture was cooled, filtered, and the filter cake washed with acetone (50 mL). The salt was further purified by suspending the material in 2-propanol at reflux temperature, cooling to ambient temperature and filtering the solid. The pure oxalate salt of racemic tamsulosin shows a melting range of: 178-182° C. and HPLC purity: 97.24 (area %). The chiral HPLC showed it to be a mixture R and S isomers in the ratio of 50.1 to 49.9. The infrared spectrum of the oxalate salt of racemic tamsulosin as shown in FIG. 1 of the drawing accompanying this specification, exhibited peaks at cm−1: 1154 & 1332 (SO2), 3408 (—NH2), 2983 (NH2+), 1591 (COO—). The 1H-NMR spectrum in CD3SOCD3 gave signals at δ values: 1.06-1.08 (3H, d, >CH—CH3), 1.30-1.33 (3H, t, —CH2—CH3), 3.89 (3H, s, —OCH3), 4.15-4.36 (10 H, 4-CH2, —CH, —NH), 7.61 (2H, s, —NH2), 6.8-7.5 (7H, m, Ar—H).

後処理

  1. temperatureThe reaction mixture was cooled
  2. filtrationthe catalyst was filtered off
  3. additionTo the filtrate containing racemic tamsulosin, oxalic acid (14.3 gm)
  4. additionwas added
  5. distillationthe solvent was distilled off
  6. additionTo the residue, acetone (700 mL) was added
  7. temperatureat reflux temperature for 30 mins
  8. temperatureThe mixture was cooled
  9. filtrationfiltered
  10. washthe filter cake washed with acetone (50 mL)
  11. customThe salt was further purified
  12. temperatureat reflux temperature
  13. filtrationfiltering the solid
  14. customThe 1H-NMR spectrum in CD3SOCD3 gave signals at δ values

出典と根拠

ORDレコード
ord-159c19aadc114f68b74757f601c8c402
出典データセット
uspto-grants-2007_07
特許番号
US07238839B2

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