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

HRID 1724197
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HRID 1724197 반응식
[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
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참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-3dd44f643db94eaf895354da1752e6e7
출처 데이터셋
uspto-grants-2009_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07485732B2

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