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

HRID 391837
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HRID 391837 반응식
[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
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참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 67898654NMP diglyme용매2회

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온도
150 °C

실험 절차

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 saturated 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).

후처리

  1. additionwas added all at once via syringe
  2. customthe reaction was removed
  3. temperaturefrom heating
  4. temperaturecooled
  5. additionpoured onto saturated ammonium chloride and EtOAc
  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)

출처 및 근거

ORD 기록
ord-7ad222d3ddda43c19a63a3c9940a4622
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08383644B2

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