Hydrochloric Acid → (R)-7-(2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)-1-hydroxyethyl)-5-hydroxybenzo[d]thiazol-2(3H)-one

HRID 1426881ノート

反応式

HRID 1426881 の反応式
C([O:5][C:6]1[CH:7]=[C:8]([C@@H:19]([OH:37])[CH2:20][NH:21][C:22]([CH3:36])([CH3:35])[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:26][CH:25]=2)[C:9]2[S:13][C:12]([O:14]C(C)C)=[N:11][C:10]=2[CH:18]=1)(C)(C)C.Cl.[OH-].[Na+]>C(O)(C)C.O>[CH2:31]([O:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:23][C:22]([NH:21][CH2:20][C@@H:19]([C:8]2[C:9]3[S:13][C:12](=[O:14])[NH:11][C:10]=3[CH:18]=[C:6]([OH:5])[CH:7]=2)[OH:37])([CH3:35])[CH3:36])=[CH:25][CH:26]=1)[CH2:32][CH2:33][CH3:34]

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86696597(R)-1-(5-tert-butoxy-2-isopropoxybenzo[d]thiazol-7-yl)-2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)ethanol

生成物 1

HCID 71294925(R)-7-(2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)-1-hydroxyethyl)-5-hydroxybenzo[d]thiazol-2(3H)-one

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 3776Isopropanol溶媒

反応条件

温度
60 °C

実験手順

To (R)-1-(5-tert-butoxy-2-isopropoxybenzo[d]thiazol-7-yl)-2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)ethanol (7.5 g) in isopropanol (30 ml) and water (25 ml) was added 1M HCl aqueous solution (43 ml). The reaction mixture was then heated to 60° C. and stirred for 2.5 h. The mixture was cooled to 50° C., and then 2M NaOH aqueous solution (18 ml) was added slowly to adjust pH between 8.2-8.4. The reaction mixture was then cooled to 30° C., followed by extraction with TBME (first time with 40 ml, the second time with 25 ml). Two organic layers were combined and washed with water (38 ml for two times) before drying with anhydrous Na2SO4. After filtration, the filtrate was concentrated, and then dissolved in MeCN (145 ml). The solution was treated with active carbon (0.6 g) and heated to 60° C. After a second filtration, the cake was washed with MeCN (10 ml for two times), the filtrate was crystallized at 60° C. to gain (R)-7-(2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)-1-hydroxyethyl)-5-hydroxybenzo[d]thiazol-2(3H)-one (3.8 g). e.e.=97.6%.

後処理

  1. temperatureThe mixture was cooled to 50° C.
  2. temperatureThe reaction mixture was then cooled to 30° C.
  3. extractionfollowed by extraction with TBME (first time with 40 ml
  4. washwashed with water (38 ml for two times)
  5. dry with materialbefore drying with anhydrous Na2SO4
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated
  8. dissolutiondissolved in MeCN (145 ml)
  9. additionThe solution was treated with active carbon (0.6 g)
  10. temperatureheated to 60° C
  11. filtrationAfter a second filtration
  12. washthe cake was washed with MeCN (10 ml for two times)
  13. customthe filtrate was crystallized at 60° C.

出典と根拠

ORDレコード
ord-0135da1876ae4d699af5935cbccd59fe
出典データセット
uspto-grants-2015_01
特許番号
US08933108B2

反応ノート

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