Acetaldehyde → 1-{5-[5-(4-Isopropoxyphenoxy)-1,3,4-thiadiazol-2-yl]thien-2-yl}ethanol

HRID 404890ノート

反応式

HRID 404890 の反応式
[CH:1]([O:4][C:5]1[CH:21]=[CH:20][C:8]([O:9][C:10]2[S:11][C:12]([C:15]3[S:16][CH:17]=[CH:18][CH:19]=3)=[N:13][N:14]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].C([Li])CCC.[CH:27](=[O:29])[CH3:28].Cl>O1CCCC1>[CH:1]([O:4][C:5]1[CH:21]=[CH:20][C:8]([O:9][C:10]2[S:11][C:12]([C:15]3[S:16][C:17]([CH:27]([OH:29])[CH3:28])=[CH:18][CH:19]=3)=[N:13][N:14]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2]

参加物

6

反応物 4

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 694379032-(4-Isopropoxyphenoxy)-5-thien-2-yl-1,3,4-thiadiazoleHCID 178418339Butyllithium

生成物 1

HCID 694341721-{5-[5-(4-Isopropoxyphenoxy)-1,3,4-thiadiazol-2-yl]thien-2-yl}ethanol収率 185.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A solution of Example 24D (0.35 g, 1.1 mmol) in tetrahydrofuran (14 mL) was cooled to −78° C. under a nitrogen atmosphere and was treated with n-butyllithium (2.5M in hexanes, 0.925 mL, 2.31 mmol) drop wise over 5 minutes. After stirring at −78° C. for 10 min, acetaldehyde (0.309 mL, 5.5 mmol) was added and the reaction was allowed to warm to −30° C. The reaction was stirred for 10 min at −30° C. and 1N HCl (20 mL) was added. The resulting bilayer was stirred at 25° C. for 5 min and was extracted with ethyl ether (80 mL). The organic phase was washed with brine (20 mL), dried (Na2SO4), filtered, and evaporated to provide 0.74 g of a light brown oil. The residue was purified by flash chromatography on silica gel eluting with a solvent gradient from 10% to 35% ethyl acetate in hexanes to provide 0.34 g (86%) of the title compound as a pale green oil. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.48 (d, J=3.68 Hz, 1H) 7.39 (d, J=9.19 Hz, 2H) 7.02 (d, J=9.19 Hz, 2H) 6.96 (dd, J=3.68, 0.74 Hz, 1H) 5.78 (d, J=5.15 Hz, 1H) 4.88-5.06 (m, 1H) 4.63 (heptet, J=5.88 Hz, 1H) 1.43 (d, J=6.25 Hz, 3H) 1.28 (d, J=5.88 Hz, 6H); MS (ESI) m/z 363 (M+H)+.

後処理

  1. temperatureto warm to −30° C
  2. stirringThe reaction was stirred for 10 min at −30° C.
  3. stirringThe resulting bilayer was stirred at 25° C. for 5 min
  4. extractionwas extracted with ethyl ether (80 mL)
  5. washThe organic phase was washed with brine (20 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated

出典と根拠

ORDレコード
ord-d4761b64c48a4078a83be3f9acdb5440
出典データセット
uspto-grants-2014_06
特許番号
US08748627B2

反応ノート

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