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

HRID 2409990ノート

反応式

HRID 2409990 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-cbfdb24e08e747bf9b1220270f5ae3f4
出典データセット
uspto-grants-2014_08
特許番号
US08815903B2

反応ノート

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