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Sodium hydride → (R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxine-6-carbonitrile

HRID 879738
ノート
印刷プレビュー

反応式

HRID 879738 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]([OH:25])[CH2:14][O:15][C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=2F)[C:19]#[N:20])=[CH:9][CH:8]=1.[H-].[Na+]>CN1C(=O)CCC1.COCCOCCOC>[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C@H:13]2[O:25][C:23]3[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=3[O:15][CH2:14]2)=[CH:9][CH:8]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 24758Sodium hydrideHCID 583270913-{(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-hydroxy-ethoxy}-4-fluoro-benzonitrile

生成物 1

HCID 58327239(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxine-6-carbonitrile収率 53.5%

試薬・触媒・溶媒 1

HCID 67898654NMP diglyme溶媒2 回

反応条件

温度
150 °C

実験手順

3-{(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-hydroxy-ethoxy}-4-fluoro-benzonitrile (10.2 g) was dissolved in 108 mL NMP-diglyme (1:9) under nitrogen and heated to 150° C. internal temperature. A suspension of sodium hydride (1130 mg of 60% NaH in mineral oil) in 10 mL NMP-diglyme (1:9) was added all at once via syringe while stirring. After 2 minutes, the reaction was removed from heating and cooled, then poured onto saturuated ammonium chloride and EtOAc. The layers were separated and the organic layer washed 3 times with 1 N HCl and dried over Na2SO4. The residue was purified by silica gel flash chromatography (DCM-hexanes 1:1 to DCM). The residue was crystallized from refluxing MeOH/DCM (about 3:1), to give 5.2 g of desired product. 1H NMR (400 MHz, CDCl3): 7.53 (d, 1H), 7.45 (d, 1H), 7.34 (m, 2H), 7.27-7.24 (m, 1H), 7.22 (d, 1H) 7.18 (m, 1H), 7.0 (m, 3H), 5.12 (m, 1H), 5.04 (s, 2H), 4.37 (m, 1H), 4.03 (m, 1H).

後処理

  1. additionwas added all at once via syringe
  2. customthe reaction was removed
  3. temperaturefrom heating
  4. temperaturecooled
  5. additionpoured
  6. customThe layers were separated
  7. washthe organic layer washed 3 times with 1 N HCl
  8. dry with materialdried over Na2SO4
  9. customThe residue was purified by silica gel flash chromatography (DCM-hexanes 1:1 to DCM)
  10. customThe residue was crystallized
  11. temperaturefrom refluxing MeOH/DCM (about 3:1)

出典と根拠

ORDレコード
ord-4a855090b1d0485ca50e7c2d73029be9
出典データセット
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08987295B2

反応ノート

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