Methyl iodide → 2-t-Butoxycarbonylamino-5-cyano-6-ethylpyridine

HRID 1378705Notes

Reaction equation

HRID 1378705 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[C:11]([CH3:17])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18]I.[NH4+].[Cl-]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[C:11]([CH2:17][CH3:18])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 10704790tert-Butyl 5-cyano-6-methylpyridin-2-ylcarbamate

Product 1

HCID 189264112-t-Butoxycarbonylamino-5-cyano-6-ethylpyridineYield 77.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-t-butoxycarbonylamino-5-cyano-6-methylpyridine (0.50 g, 2.145 mmol) in dry THF (15 ml) at -78° C. was added n-BuLl (1.75 ml, 2.5M in hexanes) dropwise. The solution turned deep red upon addition of the second equivalent of base. After 0.5 h methyl iodide (0.67 ml, 10.7 mmol) was added. After 1 h half saturated NH4Cl (15 ml) was added, the layers were separated and the aqueous layer was extracted with EtOAc (2×35 ml). The organic layers were combined and washed with saturated NaHCO3 (1×15 ml), water (1×15 ml), and brine (1×15 ml), dried over MgSO4, filtered and concentrated to an oil. The crude product was purified by flash column chromatography (95:5; hexanes: ethyl acetate) to give the title compound (0.41 g) as a solid: 1H NMR (CDCl3) δ 1.29 (t, J=7.5 Hz, 3 H), 1.53 (s, 9 H), 2.91 (q, J=7.6 Hz, 2 H), 7.40 (br s, 1H), 7.81 (d, J=8.6 Hz, 1 H), 7.87 (d, J=8.8 Hz, 1 H).

Workup

  1. additionThe solution turned deep red upon addition of the second equivalent of base
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×35 ml)
  4. washwashed with saturated NaHCO3 (1×15 ml), water (1×15 ml), and brine (1×15 ml)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to an oil
  8. customThe crude product was purified by flash column chromatography (95:5; hexanes: ethyl acetate)

Sources & evidence

ORD record
ord-c29f26829e1d4b5ea8bf5f0115623e5a
Source dataset
uspto-grants-1997_09
Patent number
US05668289

Reaction notes

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