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Hydrochloric Acid → 3-(5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxyphenyl)-3-oxopropionic acid ethyl ester

HRID 391243
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HRID 391243 반응식
[Cl-].[Mg+2].[Cl-].[C:4]([O:10][CH2:11][CH3:12])(=[O:9])[CH2:5][C:6]([O-:8])=O.[K+].[Cl:14][C:15]1[C:16]([F:34])=[C:17]([CH:31]=[CH:32][CH:33]=1)[CH2:18][C:19]1[C:20]([O:29][CH3:30])=[CH:21][C:22]([F:28])=[C:23]([CH:27]=1)C(Cl)=O.Cl>O1CCCC1.C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:11]([O:10][C:4](=[O:9])[CH2:5][C:6]([C:23]1[CH:27]=[C:19]([CH2:18][C:17]2[CH:31]=[CH:32][CH:33]=[C:15]([Cl:14])[C:16]=2[F:34])[C:20]([O:29][CH3:30])=[CH:21][C:22]=1[F:28])=[O:8])[CH3:12]
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참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium ChlorideHCID 575728405-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoyl chloride

생성물 1

HCID 575728593-(5-(3-Chloro-2-fluorobenzyl)-2-fluoro-4-methoxyphenyl)-3-oxopropionic acid ethyl ester

시약·촉매·용매 3

HCID 1140
Toluene
용매
2회
HCID 8028Tetrahydrofuran용매
HCID 8471Triethylamine용매

실험 절차

Triethylamine (9.71 g) and magnesium chloride (7.61 g) were successively added to a suspension of potassium ethyl malonate (10.8 g) in tetrahydrofuran with stirring at room temperature. After stirring at 60-70° C. for 1.5 hr, a solution of 5-(3-chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoyl chloride prepared in Step V in toluene was added dropwise, and the mixture was further stirred for 30 min. After cooling, toluene (50 ml) and 2N hydrochloric acid (60 ml) were added to the reaction mixture, and the mixture was stirred for 1 hr. The organic layer was washed successively with water (50 ml), 5% sodium hydrogencarbonate (50 ml, twice), and water (50 ml) again, and the organic layer was concentrated under reduced pressure. Toluene (50 ml) was added to the residue, and the mixture was concentrated under reduced pressure. The residue was dissolved in toluene (50 ml) to give a solution of 3-(5-(3-chloro-2-fluorobenzyl)-2-fluoro-4-methoxyphenyl)-3-oxopropionic acid ethyl ester in toluene. This was identified as the title compound by HPLC.

후처리

  1. stirringAfter stirring at 60-70° C. for 1.5 hr
  2. stirringthe mixture was further stirred for 30 min
  3. temperatureAfter cooling
  4. stirringthe mixture was stirred for 1 hr
  5. washThe organic layer was washed successively with water (50 ml), 5% sodium hydrogencarbonate (50 ml
  6. concentrationtwice), and water (50 ml) again, and the organic layer was concentrated under reduced pressure
  7. additionToluene (50 ml) was added to the residue
  8. concentrationthe mixture was concentrated under reduced pressure
  9. dissolutionThe residue was dissolved in toluene (50 ml)

출처 및 근거

ORD 기록
ord-45b765037a4f40bab4824c04ebe83af3
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08383819B2

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