Water → (9-(3-(2-Hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 446459ノート

反応式

HRID 446459 の反応式
Cl.[CH:2]([C:5]1[S:6][CH:7]=[C:8]([C:10]([N:12]2[CH2:17][C:16]3([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[O:15][CH2:14][CH2:13]2)=[O:11])[N:9]=1)([CH3:4])[CH3:3].Br[CH2:24][CH2:25][C:26]1[CH:27]=[C:28]([CH2:32][CH2:33][OH:34])[CH:29]=[CH:30][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].O>C(#N)C.CCOC(C)=O>[OH:34][CH2:33][CH2:32][C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=1)[CH2:25][CH2:24][N:20]1[CH2:19][CH2:18][C:16]2([O:15][CH2:14][CH2:13][N:12]([C:10]([C:8]3[N:9]=[C:5]([CH:2]([CH3:4])[CH3:3])[S:6][CH:7]=3)=[O:11])[CH2:17]2)[CH2:22][CH2:21]1

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 581685432-(3-(2-Bromoethyl)phenyl)ethanolHCID 66964119(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride

生成物 1

HCID 58168488(9-(3-(2-Hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone収率 88%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

To a suspension of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride in a solution of 2-(3-(2-bromoethyl)phenyl)ethanol (1.15 molar equivalents) in acetonitrile (10 volumes) at room temp was added potassium carbonate (4 molar equivalents) followed by water (0.167 volumes. The mixture was stirred at 60° C. for 66 hours, cooled to room temp, filtered, washed with MeCN and concentrated in vacuo to leave a crude orange gum. This gum was dissolved in EtOAc (3 volumes) and washed with 2N HCl (1.1 molar equivalents). The aqueous layer was basified using 2N NaOH (1.5 molar equivalents) and extracted with TBME (2×2 volumes) [an oil appeared at the interface which would not dissolve in TBME]. The combined organics and oil were diluted with EtOAc (1 volume) [oil dissolved], dried (Na2SO4), filtered and concentrated in vacuo to leave an orange gum. Yield: 88% of theoretical.

後処理

  1. temperaturecooled to room temp
  2. filtrationfiltered
  3. washwashed with MeCN
  4. concentrationconcentrated in vacuo
  5. customto leave a crude orange gum
  6. washwashed with 2N HCl (1.1 molar equivalents)
  7. extractionextracted with TBME (2×2 volumes) [an oil
  8. dissolutiondissolve in TBME]
  9. additionThe combined organics and oil were diluted with EtOAc (1 volume) [oil dissolved]
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto leave an orange gum

出典と根拠

ORDレコード
ord-3c580f1cfe9e4a2e81f220f11c3cac23
出典データセット
uspto-grants-2013_07
特許番号
US08476265B2

反応ノート

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