Hexane → (4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

HRID 1874305

反応式

HRID 1874305 の反応式
Br[C:2]1[CH:7]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:5]=[C:4]([F:15])[CH:3]=1.[F:16][C:17]1[CH:28]=[CH:27][C:20]([C:21](N(OC)C)=[O:22])=[CH:19][C:18]=1[O:29][CH:30]([CH3:32])[CH3:31].[Li]CCCC.CCCCCC>C1COCC1>[F:16][C:17]1[CH:28]=[CH:27][C:20]([C:21]([C:2]2[CH:7]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:5]=[C:4]([F:15])[CH:3]=2)=[O:22])=[CH:19][C:18]=1[O:29][CH:30]([CH3:32])[CH3:31]

参加物

6

反応物 4

HCID 8058HexaneHCID 236551051-Bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzeneHCID 59459043Benzamide,4-fluoro-N-methoxy-N-methyl-3-(1-methylethoxy)-HCID 178418339Butyllithium

生成物 1

HCID 59459304(4-Fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-76 °C

実験手順

A 3-liter four neck round-bottomed flask (flame dried) was charged 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (72.88 g, 0.25 mol), 4-fluoro-3-isopropoxy-N-methoxy-N-methylbenzamide (60.39 g, 0.25 mol) and dry THF (700 mL) under N2. The solution was cooled to −76° C., and a solution of n-BuLi in hexane (2.5M, 100 mL, 0.25 mol) was drop-wise maintaining the reaction mixture temperature below −70° C. over a period of 40 min. The reaction mixture was stirred at −76° C. for 1.5 h then quenched with 1N HCl (500 mL). The mixture was concentrated in vacuo to half the volume and was partitioned between EtOAc and H2O (v/v 1:0.3, 1 L). The organic phase was separated and the aqueous layer was extracted with EtOAc (500 mL). The combined organic extracts were washed with brine and then concentrated in vacuo to give a yellow oil which was purified by column chromatography using CH2Cl2 in hexanes (0% to 20%) to give (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as a colorless oil contaminated with a by-product (49.0 g, 50%). LC-MS (10-90% MeOH in H2O with 0.1% TFA in a 2-min gradient) 393.2 (M+H), retention time=2.15 min.

後処理

  1. customthen quenched with 1N HCl (500 mL)
  2. concentrationThe mixture was concentrated in vacuo to half the volume
  3. customwas partitioned between EtOAc and H2O (v/v 1:0.3, 1 L)
  4. customThe organic phase was separated
  5. extractionthe aqueous layer was extracted with EtOAc (500 mL)
  6. washThe combined organic extracts were washed with brine
  7. concentrationconcentrated in vacuo
  8. customto give a yellow oil which
  9. customwas purified by column chromatography

出典と根拠

ORDレコード
ord-a49b0cdbf18948b4aa02d19bfb443f17
出典データセット
uspto-grants-2012_11
特許番号
US08304403B2

関連ノート

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