Sodium hydride → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloro-4-methylpyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1508505ノート

反応式

HRID 1508505 の反応式
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[NH:15][C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].[Br:24][C:25]1[C:26]([CH2:33]Br)=[N:27][C:28]([Cl:32])=[CH:29][C:30]=1[CH3:31]>C1COCC1>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:33][C:26]3[C:25]([Br:24])=[C:30]([CH3:31])[CH:29]=[C:28]([Cl:32])[N:27]=3)[C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-oneHCID 772307103-Bromo-2-(bromomethyl)-6-chloro-4-methylpyridine

生成物 1

HCID 86704597(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloro-4-methylpyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (30.6 g, 98 mmol) in THF (800 mL) was added NaH (60% dispersion in mineral oil) (3.35 g, 84 mmol). After stirring the reaction at room temperature for 10 minutes, 3-bromo-2-(bromomethyl)-6-chloro-4-methylpyridine (16.7 g, 55.8 mmol) was added as a solution in THF (300 mL). The reaction was stirred at room temperature for 16 hours and then quenched with saturated NH4Cl (200 mL). The mixture was diluted with EtOAc (1 L). The organic layer was separated, washed with water (500 mL) and brine (500 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 0 to 50% EtOAc/heptanes afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloro-4-methylpyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one. LCMS=530.8, 532.8 (M+H)+ 1H NMR (CDCl3, 500 MHz) δ 7.89 (s, 1H), 7.81 (s, 2H), 7.18 (s, 1H), 5.87 (d, J=8.3 Hz, 1H), 5.04 (d, J=17.2 Hz, 1H), 4.42 (m, 1H), 4.32 (d, J=17.3 Hz, 1H), 2.43 (s, 3H), 0.80 (d, J=6.6 Hz, 3H).

後処理

  1. customthe reaction at room temperature for 10 minutes
  2. stirringThe reaction was stirred at room temperature for 16 hours
  3. customquenched with saturated NH4Cl (200 mL)
  4. additionThe mixture was diluted with EtOAc (1 L)
  5. customThe organic layer was separated
  6. washwashed with water (500 mL) and brine (500 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the residue by flash chromatography on silica gel with 0 to 50% EtOAc/heptanes

出典と根拠

ORDレコード
ord-3d8cc0ec02664b4e9eb8066d4f5d7b30
出典データセット
uspto-grants-2015_12
特許番号
US09221834B2

反応ノート

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