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

HRID 1724197Notes

Reaction equation

HRID 1724197 reaction equation
[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

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-3dd44f643db94eaf895354da1752e6e7
Source dataset
uspto-grants-2009_02
Patent number
US07485732B2

Reaction notes

Loading…