Sodium hydride → Chloro-6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidine

HRID 2200786노트

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HRID 2200786 반응식
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[Cl:12][C:13]1[CH:18]=[C:17](Cl)[N:16]=[C:15]([C:20]([F:23])([F:22])[F:21])[N:14]=1.[H-].[Na+]>O1CCCC1>[Cl:12][C:13]1[CH:18]=[C:17]([O:11][CH:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)[N:16]=[C:15]([C:20]([F:22])([F:23])[F:21])[N:14]=1

참가 물질

5

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HCID 24758Sodium hydrideHCID 5673521,4-Dioxaspiro(4.5)decan-8-olHCID 157131974,6-Dichloro-2-trifluoromethylpyrimidine

생성물 1

HCID 86676919Chloro-6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidine수율 68.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

1,4-Dioxaspiro[4.5]decan-8-ol (3.64 g, 23.0 mmol, Acros Organics) and 4,6-dichloro-2-(trifluoromethyl)pyrimidine (5.00 g, 23.0 mmol SynChem, Inc.) were dissolved in tetrahydrofuran (41 mL) in a vial and cooled to 0° C. A 60% mixture of sodium hydride in oil (1.10 g, 27.5 mmol, Aldrich) was added. The reaction was stirred for 30 minutes at 0° C. and at 25° C. for 60 hours at which time TLC analysis showed that most of the starting material had been consumed. The reaction was quenched with water, and was extracted with ethyl acetate and the organic extracts were washed with water, saturated NaCl, dried (MgSO4) and stripped in vacuo. The product was purified by silica gel chromatography using 10-20% ethyl acetate (EtOAc)/hexanes to give the product 4-113 chloro-6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidine as a white solid (5.35 g). 1H NMR (400 MHz, CDCl3) δ: 6.90 (s, 1H), 5.35 (m, 1H), 3.95 (s, 4H), 1.60-2.05 (m, 8H).

후처리

  1. customhad been consumed
  2. customThe reaction was quenched with water
  3. extractionwas extracted with ethyl acetate
  4. washthe organic extracts were washed with water, saturated NaCl
  5. dry with materialdried (MgSO4)
  6. customThe product was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-846ed0ad1744470f9b1c6d6f8c1fa30f
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359358B2

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