Hydrochloric Acid → Ethyl 3-(4-chlorophenyl)-3-cyclopropyl-3-hydroxypropanoate

HRID 561427ノート

反応式

HRID 561427 の反応式
C([Li])CCC.C[Si](C)(C)N[Si](C)(C)C.[CH:15]1([C:18]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[O:19])[CH2:17][CH2:16]1.Cl.[C:28]([O:31][CH2:32][CH3:33])(=[O:30])[CH3:29]>CCCCCC.O1CCCC1>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([C:18]([CH:15]2[CH2:16][CH2:17]2)([OH:19])[CH2:29][C:28]([O:31][CH2:32][CH3:33])=[O:30])=[CH:25][CH:24]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 8857Ethyl Acetate2 回HCID 13838HexamethyldisilazaneHCID 811484-Chlorophenyl cyclopropyl ketoneHCID 178418339Butyllithium

生成物 1

HCID 12168030Ethyl 3-(4-chlorophenyl)-3-cyclopropyl-3-hydroxypropanoate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒

反応条件

温度
0 °C

実験手順

13.8 ml (22.14 mmol) of a 1.6N solution of n-butyllithium in hexane were added dropwise to a solution of 4.7 ml (22.14 mmol) of hexamethyldisilazane in 17 ml of tetrahydrofuran at −20° C., and the mixture was stirred at 0° C. for 30 min and then cooled again to −78° C. 2.17 ml (22.14 mmol) of ethyl acetate were added, and the mixture was stirred for 30 min and, after addition of 2.00 g (11.07 mmol) of 4-chlorophenyl cyclopropyl ketone, dissolved in 17 ml of tetrahydrofuran, stirred at −78° C. for a further hour. The reaction solution was mixed with 1N hydrochloric acid and ethyl acetate, and the phases were separated. The organic phase was washed successively with 0.5N hydrochloric acid, water and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. After purification of the crude product by preparative HPLC (mobile phase: acetonitrile/water gradient) the acetonitrile was removed in a rotary evaporator, and the aqueous phase was extracted several times with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. 2.54 g (99% of theory) of the title compound were obtained.

後処理

  1. temperaturecooled again to −78° C
  2. stirringthe mixture was stirred for 30 min
  3. stirringstirred at −78° C. for a further hour
  4. customthe phases were separated
  5. washThe organic phase was washed successively with 0.5N hydrochloric acid, water and saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customAfter purification of the crude product by preparative HPLC (mobile phase: acetonitrile/water gradient) the acetonitrile
  10. customwas removed in a rotary evaporator
  11. extractionthe aqueous phase was extracted several times with diethyl ether
  12. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

出典と根拠

ORDレコード
ord-14e6075707d54b7981be63286fee5ef3
出典データセット
uspto-grants-2011_11
特許番号
US08063234B2

反応ノート

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