Methyl 2-(3,5-difluorophenyl)acetate → Methyl{1-[bis(4-chlorophenyl)methyl]-3-hydroxyazetidin-3-yl}(3,5-difluorophenyl)acetate

HRID 602653ノート

反応式

HRID 602653 の反応式
C([Li])CCC.[F:6][C:7]1[CH:8]=[C:9]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:10]=[C:11]([F:13])[CH:12]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[N:27]2[CH2:30][C:29](=[O:31])[CH2:28]2)=[CH:22][CH:21]=1>CCCCCC.C1COCC1>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[N:27]2[CH2:28][C:29]([CH:14]([C:9]3[CH:8]=[C:7]([F:6])[CH:12]=[C:11]([F:13])[CH:10]=3)[C:15]([O:17][CH3:18])=[O:16])([OH:31])[CH2:30]2)=[CH:22][CH:21]=1

参加物

6

反応物 3

HCID 22270748Methyl 2-(3,5-difluorophenyl)acetateHCID 225066481-[Bis(4-chlorophenyl)methyl]azetidin-3-oneHCID 178418339Butyllithium

生成物 1

HCID 67055297Methyl{1-[bis(4-chlorophenyl)methyl]-3-hydroxyazetidin-3-yl}(3,5-difluorophenyl)acetate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒3 回HCID 8058Hexane溶媒

反応条件

温度
-78 °C

実験手順

A solution of 2 mL of 1.6M butyllithium in hexane and 2 mL of dry THF was cooled to −78° C. under nitrogen. To this was added a solution of 0.626 g (3.2 mmol) of methyl (3,5-difluorophenyl)acetate in 4 mL of THF and the solution was stirred at −78° C. After 20 min, a solution of 0.600 g (1.95 mmol) of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one in 4 mL THF was added and the solution was stirred at −78° C. After 1 h, the reaction was quenched by addition of 10 mL of saturated NH4Cl solution and 20 mL of ether. The layers were separated and the aqueous layer was washed with ether. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated. The residue was filtered through a plug of silica gel using 25% ether-hexane to afford the title compound; 1NMR (CDCl3) δ 2.91 (d, 1H J=8.3 Hz), 3.14 (d, 1H J=8.0 Hz), 3.17 (d, 2H, J=8.2 Hz), 3.32 (d, 1H J=7.8 Hz), 3.74 (s, 3H), 4.03 (s, br, 1H), 4.42 (s, 1H), 4.42 (s, 1H), 6.76 (m, 1H), 6.6.89 (m, 2H), 7.33 (m, 4H), 7.38 (m, 4H); Mass Spectrum: m/e=492 (M+1 35Cl, 35Cl) and 494 (M+1 35Cl, 37Cl).

後処理

  1. stirringthe solution was stirred at −78° C
  2. waitAfter 1 h
  3. customthe reaction was quenched by addition of 10 mL of saturated NH4Cl solution and 20 mL of ether
  4. customThe layers were separated
  5. washthe aqueous layer was washed with ether
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. filtrationThe residue was filtered through a plug of silica gel using 25% ether-hexane

出典と根拠

ORDレコード
ord-4ed6c0e481454be394d462d227a74c61
出典データセット
uspto-grants-2011_03
特許番号
US07906503B2

反応ノート

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