Phosphorus oxychloride → 3-{1-[Bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-3-(3,5-difluorophenyl)-2,2-dimethylpropanenitrile

HRID 602667Notes

Reaction equation

HRID 602667 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:9]2[CH2:12][CH:11]([C:13]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)(O)[C:14]([CH3:18])([CH3:17])[C:15]#[N:16])[CH2:10]2)=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[N:9]2[CH2:12][C:11](=[C:13]([C:20]3[CH:21]=[C:22]([F:27])[CH:23]=[C:24]([F:26])[CH:25]=3)[C:14]([CH3:18])([CH3:17])[C:15]#[N:16])[CH2:10]2)=[CH:33][CH:32]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 670658733-{1-[Bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-(3,5-difluorophenyl)-3-hydroxy-2,2-dimethylpropanenitrile

Product 1

HCID 114772303-{1-[Bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-3-(3,5-difluorophenyl)-2,2-dimethylpropanenitrile

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

The reaction mixture of 128 mg (0.255 mmol) of 3-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-(3,5-difluorophenyl)-3-hydroxy-2,2-dimethylpropanenitrile and 3 mL of phosphorus oxychloride in 5 mL of pyridine was heated at reflux for 48 h. The solution was concentrated, poured into 30 mL of ether, and washed with 5 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=4:1 to afford the title compound. 1NMR (CDCl3) δ 1.47 (s, 6H), 3.48 (s, 2H), 4.18 (s, 2H), 4.47 (s, 1H), 6.66-6.77 (m, 2H), 7.25-6-7.35 (r, 8H); Mass Spectrum: m/e=483 (M+1 35Cl, 35Cl) and 485 (M+1 35Cl, 37Cl).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 48 h
  3. concentrationThe solution was concentrated
  4. additionpoured into 30 mL of ether
  5. washwashed with 5 mL of aq NaHCO3
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate=4:1

Sources & evidence

ORD record
ord-704167086c4a487c8d8f806ff6adcb6b
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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