Dimethylformamide → HCID 58528867, compound

HRID 1431017Notes

Reaction equation

HRID 1431017 reaction equation
[H-].[Na+].[I:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.CN(C=O)C.F[C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([S:25][C:26]2[N:27]([CH3:31])[CH:28]=[CH:29][N:30]=2)[CH:24]=1)[C:20]#[N:21]>CCOCC.[OH-].[Na+]>[I:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:17]2[CH:18]=[C:19]([CH:22]=[C:23]([S:25][C:26]3[N:27]([CH3:31])[CH:28]=[CH:29][N:30]=3)[CH:24]=2)[C:20]#[N:21])=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 108944-IodophenolHCID 24758Sodium hydrideHCID 585288273-Fluoro-5-[(1-methyl-1H-imidazol-2-yl)thio]benzonitrile

Product 1

HCID 58528867HCID 58528867, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of NaH (60%, 312 mg, 7.8 mmol) in oil was rinsed with dry pentane by syringe (3×3 mL) and excess solvent removed under a steam of N2. Solid 4-iodophenol (1.72 g, 7.8 mmol) was added followed by 16 mL of DMF under ice-bath cooling which resulted in a vigorous evolution of gas. After 15 min, solid 3-fluoro-5-(1-methyl-1H-imidazol-2-ylsulfanyl)-benzonitrile (910 mg, 3.9 mmol) was added and the resulting mixture microwave heated at 160° C. for 10 min. After cooling to rt, the mixture was diluted with ether and 3 M aqueous NaOH and shaken. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. The resulting 1.8 g of residue was adsorbed to 4.5 g SiO2 from CH2Cl2 and subjected to MPLC on a 40 g column of SiO2 eluting with % EtOAc in hexanes (time): 33% (10 min), 35-50% (20 min ramp) which provided 1.60 g (95%) of the title compound: 1H NMR (500 MHz, DMSO-d6): δ 3.63 (s, 3H), 6.82 (dd, 1H, J=2, 1 Hz), 6.90 (d, 2H, J=8 Hz), 7.13 (d, 1H, J=1 Hz), 7.26 (t, 1H, J=2 Hz), 7.37 (dd, 114, J=2, 1 Hz), 7.50 (d, 1H, J=1 Hz), 7.75 (d, 2H, J=8 Hz); LCMS (m/z): 434.3 [C17H12IN3OS+H]+.

Workup

  1. washwas rinsed with dry pentane by syringe (3×3 mL) and excess solvent
  2. customremoved under a steam of N2
  3. temperaturecooling which
  4. customresulted in a vigorous evolution of gas
  5. temperatureAfter cooling to rt
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried (MgSO4)
  8. customevaporated

Sources & evidence

ORD record
ord-f00e2c72f8db41d0be7e9e783789a188
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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