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Cesium carbonate → (2-Ethylthiazol-4-yl)(9-(4-(2-hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

HRID 446426
ノート
印刷プレビュー

反応式

HRID 446426 の反応式
Br[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][OH:12])=[CH:6][CH:5]=1.FC(F)(F)C(O)=O.[CH2:20]([C:22]1[S:23][CH:24]=[C:25]([C:27]([N:29]2[CH2:34][C:33]3([CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)[O:32][CH2:31][CH2:30]2)=[O:28])[N:26]=1)[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.O>[CH2:20]([C:22]1[S:23][CH:24]=[C:25]([C:27]([N:29]2[CH2:34][C:33]3([CH2:39][CH2:38][N:37]([CH2:2][CH2:3][C:4]4[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][OH:12])=[CH:6][CH:5]=4)[CH2:36][CH2:35]3)[O:32][CH2:31][CH2:30]2)=[O:28])[N:26]=1)[CH3:21]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 669633682-(4-(2-Bromoethyl)phenyl)ethanol2 回HCID 66964094(2-Ethylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

生成物 1

HCID 58168519(2-Ethylthiazol-4-yl)(9-(4-(2-hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

試薬・触媒・溶媒 2

HCID 962Water
溶媒
HCID 13387N-methyl-2-pyrrolidone溶媒2 回

反応条件

温度
75 °C

実験手順

A solution of 2-(4-(2-bromoethyl)phenyl)ethanol [Organometallics 2002, 21(20), 4217] (1.71 g) in NMP (5 mL) was added to a suspension of (2-ethylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate [Example 3, step b] (3.0 g) and cesium carbonate (5.60 g) in NMP (10 mL) and the mixture stirred at 75° C. under nitrogen for 4 hours. More 2-(4-(2-bromoethyl)phenyl)ethanol (0.65 g) was added and the mixture stirred at 75° C. for 18 hours. The mixture was cooled, diluted with water and extracted into ethyl acetate (×3). The combined extracts were washed with 10% brine, 30% brine and saturated brine, dried over magnesium sulfate, filtered and the solvent removed. The crude product was purified by flash silica chromatography, successively eluted with 50% ethyl acetate in isohexane with 5% triethylamine, then 100% ethyl acetate with 5% triethylamine, then 10% methanol in ethyl acetate with 5% triethylamine. Fractions containing the product were evaporated to dryness to afford the subtitled compound as a yellow oil. Yield 1.90 g.

後処理

  1. stirringthe mixture stirred at 75° C. for 18 hours
  2. temperatureThe mixture was cooled
  3. extractionextracted into ethyl acetate (×3)
  4. washThe combined extracts were washed with 10% brine, 30% brine and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed
  8. customThe crude product was purified by flash silica chromatography
  9. washsuccessively eluted with 50% ethyl acetate in isohexane with 5% triethylamine
  10. additionFractions containing the product
  11. customwere evaporated to dryness

出典と根拠

ORDレコード
ord-451db4ae85a042009a960e5c3795a665
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08476265B2

反応ノート

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