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

HRID 391243
ノート
印刷プレビュー

反応式

HRID 391243 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 1140
Toluene
溶媒
2 回
HCID 8028Tetrahydrofuran溶媒
HCID 8471Triethylamine溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-45b765037a4f40bab4824c04ebe83af3
出典データセット
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08383819B2

反応ノート

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