Sodium hydride → tert-Butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-3-methyl-2-oxobutyl]-5-methoxyphenyl}carbamate

HRID 2409990Notes

Reaction equation

HRID 2409990 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])=[C:7]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:8]=1.[H-].[Na+].Cl[CH2:26][C:27]1[N:32]=[C:31]([C:33]#[N:34])[CH:30]=[CH:29][CH:28]=1.[Cl-].[NH4+]>CN(C)C=O>[C:33]([C:31]1[N:32]=[C:27]([CH2:26][CH:17]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][C:7]=2[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:18](=[O:22])[CH:19]([CH3:20])[CH3:21])[CH:28]=[CH:29][CH:30]=1)#[N:34]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 103518756-Chloromethyl-2-cyanopyridineHCID 69096724Tert-butyl (5-methoxy-2-(3-methyl-2-oxobutyl)phenyl)carbamate

Product 1

HCID 86703307tert-Butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-3-methyl-2-oxobutyl]-5-methoxyphenyl}carbamateYield 58.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under an argon atmosphere, to a solution of tert-butyl [5-methoxy-2-(3-methyl-2-oxobutyl)phenyl]carbamate (337 mg) in N,N-dimethylformamide (4 mL) was added sodium hydride (50-72% in oil, 56 mg) under ice-cooling, and the mixture was stirred for 30 minutes. 6-(Chloromethyl)pyridine-2-carbonitrile (167 mg) was added thereto, followed by stirring for 1 hour. To the reaction mixture was added a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine successively, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (271 mg). 1H-NMR (CDCl3) δ ppm: 0.91 (3H, d, J=6.5 Hz), 1.07 (3H, d, J=7.3 Hz), 1.57 (9H, s), 2.56-2.72 (1H, m), 3.18 (1H, dd, J=8.2, 15.9 Hz), 3.61 (1H, dd, J=6.8, 15.9 Hz), 3.77 (3H, s), 4.65-4.74 (1H, m), 6.58 (1H, dd, J=2.8, 8.7 Hz), 6.92 (1H, d, J=8.7 Hz), 7.22-7.29 (1H, m), 7.35 (1H, d, J=2.8 Hz), 7.46-7.60 (2H, m), 7.65 (1H, t, J=7.8 Hz).

Workup

  1. temperaturecooling
  2. stirringby stirring for 1 hour
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with water and saturated brine successively
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-cbfdb24e08e747bf9b1220270f5ae3f4
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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