Dimethylformamide → 3-{1-[(Diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorobenzonitrile

HRID 602983Notes

Reaction equation

HRID 602983 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]([CH:14]2[CH2:17][N:16]([CH:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:15]2)[C:10]([F:13])([CH3:12])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:31][N:32](C=O)C>O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:25]1([CH:18]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:16]2[CH2:15][CH:14]([CH:9]([C:4]3[CH:3]=[C:2]([CH:7]=[C:6]([F:8])[CH:5]=3)[C:31]#[N:32])[C:10]([F:13])([CH3:12])[CH3:11])[CH2:17]2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 670552993-[1-(3-Bromo-5-fluorophenyl)-2-fluoro-2-methylpropyl]-1-(diphenylmethyl)azetidine

Product 1

HCID 113390333-{1-[(Diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorobenzonitrile

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A solution of 16.19 g (34.42 mmol) of 3-[1-(3-bromo-5-fluorophenyl)-2-fluoro-2-methylpropyl]-1-(diphenylmethyl)azetidine, 3.23 g (27.53 mmol) of zinc cyanide, 1.10 g (1.2 mmol) of tris(dibenzylideneacetone)dipalladium, and 1.53 g (2.75 mmol) of DPPF in 99 mL of DMF and 1 mL of water was degassed for 1 h at rt. Then it was stirred at 140° C. After 17 h, it was concentrated to remove solvents. Then the mixture was poured into 300 mL of ether/ethyl acetate (1:1) and 100 mL aq NaHCO3. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexanes/ethyl acetate to afford the title compound as a white solid; 1H-NMR(CDCl3) δ 1.22(d, 3H, J=21 Hz), 1.30(d, 6H, J=21 Hz), 2.30 (t, 1H, J=7.8 Hz), 2.86-2.96 (m, 2H), 3.08-3.18 (m, 2H), 3.65 (t, 1H, J=7 Hz), 4.25 (s, 1H), 7.13-7.43 (m, 13H); Mass Spectrum: m/e=417 (M+1).

Workup

  1. concentrationit was concentrated
  2. customto remove solvents
  3. additionThen the mixture was poured into 300 mL of ether/ethyl acetate (1:1) and 100 mL 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

Sources & evidence

ORD record
ord-48821580f37d414dbe671d519d800a88
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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