Dichloromethane → 1-[5-(3-Chloro-2-fluorobenzyl)-2,4-dimethoxyphenyl]ethanone

HRID 332931ノート

反応式

HRID 332931 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[O:17][CH3:18])[C:3]=1[F:19].C(Cl)Cl.[Cl-].[Al+3].[Cl-].[Cl-].[C:27](Cl)(=[O:29])[CH3:28]>CC(O)C.CCCCCCC.O>[Cl:1][C:2]1[C:3]([F:19])=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][C:9]1[C:10]([O:17][CH3:18])=[CH:11][C:12]([O:15][CH3:16])=[C:13]([C:27](=[O:29])[CH3:28])[CH:14]=1

参加物

8

反応物 4

HCID 6344Dichloromethane2 回HCID 6367Acetyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 714875021-Chloro-3-(2,4-dimethoxybenzyl)-2-fluorobenzene

生成物 1

HCID 595518251-[5-(3-Chloro-2-fluorobenzyl)-2,4-dimethoxyphenyl]ethanone収率 75%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 3776Isopropanol溶媒HCID 8900Heptane溶媒

反応条件

温度
-10 °C

実験手順

The compound 5 DCM solution was transferred into a clean reactor and cooled to −13 to −7° C. Dichloromethane (6 volumes) was charged and followed by aluminum chloride (1.03 eq) while maintaining the temperature at not more than −7° C. Acetyl chloride (1.12 eq) was slowly charged to the mixture while maintaining the temperature at not more than −10° C. The reaction mixture was agitated at −13 to −7° C. and the progress of the acylation reaction was monitored by HPLC. After the acylation was completed the reaction mixture was transferred onto 5 volumes of cold (2 to 8° C.) water while maintaining the temperature at not more than 25° C. The quenched mixture was allowed to warm to 19 to 25° C. and agitated till a biphasic mixture was formed. The organic phase was separated and washed with water (3 volumes). The organic phase was separated and concentrated by vacuum distillation. The solvent was exchanged to 2-propanol by coevaporation under vacuum. The slurry formed was diluted with 2-propanol (1 volume) and then heated to reflux to form a solution. Heptane (2.9 volumes) was slowly charged to the hot solution and cooled to 0 to 5° C. to form a slurry. The product was isolated by filtration. The wet cake was washed with a mixture of 2-propanol and heptane and dried at not more than 40° C. to yield approximately 75% of compound 8 as an off-white to light pink solid. 1H NMR (CDCl3) δ 7.66 (s, 1H), 7.18 (td, 1H, J=7 Hz, 2 Hz), 6.88-6.98 (m, 2H), 6.42 (s, 1H), 3.89-3.92 (m, 5H), 3.85 (s, 3H), 2.55 (s, 3H).

後処理

  1. temperaturewhile maintaining the temperature at not more than −7° C
  2. temperaturewhile maintaining the temperature at not more than −10° C
  3. customthe progress of the acylation reaction
  4. temperaturewhile maintaining the temperature at not more than 25° C
  5. temperatureto warm to 19 to 25° C.
  6. stirringagitated till a biphasic mixture
  7. customwas formed
  8. customThe organic phase was separated
  9. washwashed with water (3 volumes)
  10. customThe organic phase was separated
  11. concentrationconcentrated by vacuum distillation
  12. customThe slurry formed
  13. temperatureheated
  14. temperatureto reflux
  15. customto form a solution
  16. temperaturecooled to 0 to 5° C.
  17. customto form a slurry
  18. customThe product was isolated by filtration
  19. washThe wet cake was washed with a mixture of 2-propanol and heptane
  20. customdried at not more than 40° C.

出典と根拠

ORDレコード
ord-bfcd84e7142a4c51a7a0bc636093a5ab
出典データセット
uspto-grants-2014_11
特許番号
US08877931B2

反応ノート

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