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

HRID 446453ノート

反応式

HRID 446453 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+]>C(#N)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

6

反応物 3

HCID 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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

A mixture of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride [Example 27, step a] (13.6 g) and 2-(3-(2-bromoethyl)phenyl)ethanol [Organometallics 2002, 21(20), 4217] (13.51 g) and potassium carbonate (21.7 g) in acetonitrile (700 mL) and water (13 mL) was heated at 60° C. for 36 hours. The solvent was decanted off and evaporated under reduced pressure. The residue was partitioned between ethyl acetate and brine, the aqueous layer was re-extracted with ethyl acetate, and the combined organic layers were dried, filtered and the solvent evaporated under reduced pressure. The residue was purified by flash silica chromatography, using 5% methanol in ethyl acetate containing 1% triethylamine as solvent. Fractions containing the product were evaporated to dryness to afford the subtitled compound. Yield 13.2 g.

後処理

  1. customThe solvent was decanted off
  2. customevaporated under reduced pressure
  3. customThe residue was partitioned between ethyl acetate and brine
  4. extractionthe aqueous layer was re-extracted with ethyl acetate
  5. customthe combined organic layers were dried
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customThe residue was purified by flash silica chromatography
  9. additionFractions containing the product
  10. customwere evaporated to dryness

出典と根拠

ORDレコード
ord-0be6952b7b9945b99756625975e58e8f
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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