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

HRID 1724197
ノート
印刷プレビュー

反応式

HRID 1724197 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]#[N:11])[CH:5]=[C:6]([F:8])[CH:7]=1.C([Li])C[CH2:14][CH3:15].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([N:29]2[CH2:32][C:31](=C(C3C=C(F)C=C(F)C=3)C(C)(O)C)[CH2:30]2)[CH2:25][CH2:26][CH2:27][CH3:28])=[CH:20][CH:19]=1.C(N(CC)C(C)C)(C)C.CS([Cl:59])(=O)=O>C1COCC1.CN(C)C1C=CN=CC=1.CCOCC>[Cl:59][C:28]1[CH:27]=[CH:26][C:25]([CH:24]([C:21]2[CH:20]=[CH:19][C:18]([Cl:17])=[CH:23][CH:22]=2)[N:29]2[CH2:30][C:31](=[C:9]([C:4]3[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=3)[C:10]#[N:11])[CH2:32]2)=[CH:15][CH:14]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 5185653,5-DifluorophenylacetonitrileHCID 112700951{-1-[1-(4-Chlorophenyl)pentyl]azetidin-3-ylidene}-1-(3,5-difluorophenyl)-2-methylpropan-2-olHCID 178418339Butyllithium

生成物 1

HCID 11316639
{1-[Bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(3,5-difluorophenyl)acetonitrile

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 540 mg (3.53 mmol) of 3,5-difluorophenylacetonitrile in 8 mL of THF a solution of 1.41 mL (3.53 mmol) of butyllithium (2.5M solution in hexanes) was added and it was stirred for 30 minutes at −78° C. Then a solution of 985 mg (3.21 mmol) of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one (1) in THF was added and it was stirred for 3 h at −78° C. Then 510 mg (4.17 mmol) of 4-dimethylaminopyridine, 840 uL(4.82 mmol) of N,N-diisopropylethylamine and 558 uL (7.06 mmol) of methanesulfonyl chloride was added and it was stirred at −78° C. to rt overnight. The solution was poured into 80 mL of ether and washed with 10 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=9:1 to afford the title compound; 1NMR(CDCl3) δ 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=430 (M+1 35Cl, 35Cl) and 432 (M+1 35Cl, 37Cl).

後処理

  1. stirringit was stirred for 3 h at −78° C
  2. stirringit was stirred at −78° C. to rt overnight
  3. washwashed with 10 mL of aq NaHCO3
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate=9:1

出典と根拠

ORDレコード
ord-3dd44f643db94eaf895354da1752e6e7
出典データセット
uspto-grants-2009_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07485732B2

反応ノート

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