Sodium Methoxide → tert-Butyl ((4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate

HRID 930382ノート

反応式

HRID 930382 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH3:27])[CH2:14][C@@H:13]([C:15]([F:18])([F:17])[F:16])[O:12][C:11]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[N:10]2)[C:5](F)=[N:6][CH:7]=1.[CH3:28][O-:29].[Na+]>>[Br:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH3:27])[CH2:14][C@@H:13]([C:15]([F:18])([F:17])[F:16])[O:12][C:11]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[N:10]2)[C:5]([O:29][CH3:28])=[N:6][CH:7]=1

参加物

3

反応物 2

HCID 10942334Sodium MethoxideHCID 86732131tert-Butyl ((4S,6S)-4-(5-bromo-2-fluoropyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate

生成物 1

HCID 86732211tert-Butyl ((4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate収率 97%

反応条件

温度
50 °C

実験手順

tert-Butyl ((4S,6S)-4-(5-bromo-2-fluoropyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate (5k, 0.500 g, 1.096 mmol, as described in Example 31, Method G, Step 9) was treated with sodium methanolate 25% MeOH (3 mL). The reaction was heated at 50° C. for 40 min. The reaction was quenched with water and methanol was removed by reduced pressure. The resulting mixture was extracted with EtOAc three times. The combined organic layers were dried on sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography using a gradient of 0-30% EtOAc/hexane to give tert-Butyl ((4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate (0.49 g, 97% yield). MS m/z=469.9 [M+H]+. Calculated for C17H21BrF3N3O4: 468.3

後処理

  1. customThe reaction was quenched with water and methanol
  2. customwas removed by reduced pressure
  3. extractionThe resulting mixture was extracted with EtOAc three times
  4. customThe combined organic layers were dried on sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by column chromatography

出典と根拠

ORDレコード
ord-cee3049363364b429deb19f3c6c968fa
出典データセット
uspto-grants-2016_03
特許番号
US09296734B2

反応ノート

読み込み中…