Sodium hydride → tert-butyl (9aR)-3-(3-cyano-4-fluorophenyl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

HRID 2175809

反応式

HRID 2175809 の反応式
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]([OH:27])[CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][C@@H:13]2[CH2:25]O)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].[H-].[Na+].S(N1C=CN=C1)(C1C=CC(C)=CC=1)(=O)=O>C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([CH:10]2[O:27][CH2:25][C@H:13]3[CH2:14][N:15]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:16][CH2:17][N:12]3[CH2:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 752191-(p-Toluenesulfonyl)imidazoleHCID 86727047tert-butyl (3R)-4-[2-(3-cyano-4-fluorophenyl)-2-hydroxyethyl]-3-(hydroxymethyl)piperazine-1-carboxylate

生成物 1

HCID 86727048tert-butyl (9aR)-3-(3-cyano-4-fluorophenyl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A solution of tert-butyl (3R)-4-[2-(3-cyano-4-fluorophenyl)-2-hydroxyethyl]-3-(hydroxymethyl)piperazine-1-carboxylate (5.0 g, 13.2 mmol) in 100 mL of THF was stirred at 0° C. for 10 min, and then NaH (60%) (1.32 g, 33.0 mmol) was added at 0° C. The resulting white suspension was stirred vigorously at 0° C. for 5 min, then at r.t for 1 h. The reaction suspension was then recooled to 0° C., N-Tosylimidazole was added and the resulting solution was stirred for a further 10 min at 0° C. before being warmed again to r.t and stirred for 1 h. The reaction solution was then cooled once more to 0° C., and excess sodium hydride was carefully quenched by the slow addition of sat. NH4Cl solution. The resulting biphasic solution was partitioned between sat. NH4Cl and EtOAc. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified with silica gel column chromatography to give the title compound: 1H-NMR (300 MHz, CDCl3) δ7.76˜7.79 (m, 1H), 7.49˜7.58 (m, 1H), 7.11˜7.15 (m, 1H), 7.16˜7.12 (m, 1H), 3.86˜4.06 (m, 2H), 3.33˜3.48 (m, 1H), 3.08˜3.17 (m, 1H), 2.80˜2.94 (m, 2H), 2.64˜2.74 (m, 2H), 2.29˜2.46 (m, 2H), 2.09˜2.20 (m, 1H), 1.40 (d, J=3.0 Hz, 9H).

後処理

  1. waitat r.t for 1 h
  2. customwas then recooled to 0° C.
  3. stirringthe resulting solution was stirred for a further 10 min at 0° C.
  4. temperaturebefore being warmed again
  5. stirringstirred for 1 h
  6. temperatureThe reaction solution was then cooled once more to 0° C.
  7. customexcess sodium hydride was carefully quenched by the slow addition of sat. NH4Cl solution
  8. customThe resulting biphasic solution was partitioned between sat. NH4Cl and EtOAc
  9. washThe organic layer was washed with water and brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated in vacuum
  12. customThe residue was purified with silica gel column chromatography

出典と根拠

ORDレコード
ord-a5c94dacd85b4e128316bf7b94987dde
出典データセット
uspto-grants-2015_06
特許番号
US09062070B2

関連ノート

読み込み中…