Methanesulfonyl chloride → Methyl {1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetate

HRID 602970ノート

反応式

HRID 602970 の反応式
[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[CH:6]=1.C([Li])CCC.[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)[CH2:28]2)=[CH:22][CH:21]=1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O>C1COCC1.CN(C)C1C=CN=CC=1.CCOCC>[Cl:38][C:35]1[CH:36]=[CH:37][C:32]([CH:26]([C:23]2[CH:22]=[CH:21][C:20]([Cl:19])=[CH:25][CH:24]=2)[N:27]2[CH2:30][C:29](=[C:4]([C:5]3[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[CH:6]=3)[C:3]([O:2][CH3:1])=[O:13])[CH2:28]2)=[CH:33][CH:34]=1

参加物

9

反応物 5

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 22270748Methyl 2-(3,5-difluorophenyl)acetateHCID 225066481-[Bis(4-chlorophenyl)methyl]azetidin-3-oneHCID 178418339Butyllithium

生成物 1

HCID 57559907Methyl {1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetate

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of 3.83 g (20.57 mmol) of methyl(3,5-difluorophenyl)acetate in 30 mL of THF was added a solution of 8.6 mL (21.51 mmol) of butyllithium (2.5M solution in hexanes) and stirred for 30 minutes at −78° C. A solution of 5.73 g (18.7 mmol) of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one in 10 mL THF was added and the solution was stirred for 2 h at −78° C. Then 2.28 g (18.6 mmol) of 4-dimethylaminopyridine, 3.3 mL(l 8.7 mmol) of DIEA and 3.0 mL (37.4 mmol) of methanesulfonyl chloride was added and the solution was stirred for 1 h as it warmed from −78° C. to rt. The reaction mixture was then warmed to 45° C. and stirred for additional 2.5 h. The mixture was poured into 250 mL of ether and washed with 50 mL of aq NaHCO3. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexanes/ethyl acetate=15:1 to afford the title compound; 1H-NMR (CDCl3) δ 3.67 (s, 3H), 3.84 (m, 2H), 4.25 (m, 2H), 4.54 (s, 1H), 6.76 (m, 1H), 6.78 (m, 2H), 7.33 (m, 3H), 7.38 (m, 2H); Mass Spectrum: m/e=474 (M+1 35Cl, 35Cl) and 476 (M+1 35Cl, 37Cl).

後処理

  1. stirringthe solution was stirred for 2 h at −78° C
  2. stirringthe solution was stirred for 1 h as it
  3. temperaturewarmed from −78° C. to rt
  4. temperatureThe reaction mixture was then warmed to 45° C.
  5. stirringstirred for additional 2.5 h
  6. washwashed with 50 mL of aq NaHCO3
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate=15:1

出典と根拠

ORDレコード
ord-7b08000781824461a2e5018a398596d0
出典データセット
uspto-grants-2011_03
特許番号
US07906652B2

反応ノート

読み込み中…