Methyl iodide → HCID 59580411, compound

HRID 1803432Notes

Reaction equation

HRID 1803432 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[S:9][C:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[C:11]([I:13])[N:12]=2)[CH:5]=[N:6][CH:7]=1.[H-].[Na+].I[CH3:25]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[S:9][C:10]([N:14]([CH3:25])[C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[C:11]([I:13])[N:12]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59580869HCID 59580869, compound

Product 1

HCID 59580411HCID 59580411, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-ylcarbamate (1.20 g, 2.85 mmol) in DMF (5.7 mL) at 0° C. was added sodium hydride (125 mg, 3.13 mmol, 60% oil suspension) and the mixture was stirred at 0° C. for 10 min. To the yellow mixture was added iodomethane (0.49 g, 3.42 mmol) and the reaction mixture was stirred at 0° C. for 30 min. The ice-water bath was removed and the mixture was stirred for an additional 1 hour. The mixture was acidified with 0.1 N aq. HCl to neutral pH and diluted with ethyl acetate (100 mL) and aqueous sodium bicarbonate (5 mL). The organic phase was separated and rinsed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a yellow residue. This residue was purified on silica gel chromatography (6:4 hexane/ethyl acetate) to give tert-butyl 2-(5-fluoropyridin-3-yl)-4-iodothiazol-5-yl(methyl)carbamate as a pale yellow solid (1.13 g, 91%): mp 70-71° C.; 1H NMR (300 MHz, CDCl3) δ 8.87 (s, 1H), 8.53 (bs, 1H), 7.99 (d, J=0.9 Hz, 1H), 3.23 (s, 3H), 1.45 (s, 9H); ESIMS m/z 436.1 (M+1).

Workup

  1. stirringthe reaction mixture was stirred at 0° C. for 30 min
  2. customThe ice-water bath was removed
  3. stirringthe mixture was stirred for an additional 1 hour
  4. additiondiluted with ethyl acetate (100 mL) and aqueous sodium bicarbonate (5 mL)
  5. customThe organic phase was separated
  6. washrinsed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a yellow residue
  11. customThis residue was purified on silica gel chromatography (6:4 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-12b6d5bb655245cb8b12361751e5837a
Source dataset
uspto-grants-2013_01
Patent number
US08350044B2

Reaction notes

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