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

HRID 561427

반응식

HRID 561427 반응식
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

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 8857Ethyl Acetate2회HCID 13838HexamethyldisilazaneHCID 811484-Chlorophenyl cyclopropyl ketoneHCID 178418339Butyllithium

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8058Hexane용매

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-14e6075707d54b7981be63286fee5ef3
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063234B2

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