Sodium Sulfite → (S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 1471107노트

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HRID 1471107 반응식
S([O-])([O-])=O.[Na+].[Na+].[I:7][C:8]1[N:9]=[C:10]([C@@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[NH:11][C:12]=1I>C(O)C.O.C(OCC)(=O)C>[I:7][C:8]1[NH:9][C:10]([C@@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[N:11][CH:12]=1

참가 물질

6

반응물 2

HCID 24437Sodium SulfiteHCID 59449990(S)-tert-butyl 2-(4,5-diiodo-1H-imidazol-2-yl)-pyrrolidine-1-carboxylate

생성물 1

HCID 58498756(S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate수율 73.1%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매2회HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

Sodium sulfite (10.31 g, 82 mmol) was added to a solution of (S)-tert-butyl 2-(4,5-diiodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (4.0 g, 8.2 mmol) in ethanol (75 mL) and water (75 mL). The suspension was heated with an oil bath at 100° C. for 4 hours and at 90° C. for 16 h. The reaction was diluted with ethyl acetate and water. The layers were separated and the aqueous layer was extracted several times with ethyl acetate. The combined organic phases were dried (brine, Na2SO4), filtered and concentrated in vacuo. The residue was purified by a flash chromatography (sample was dry loaded on silica gel and eluted with, 0 to 40% ethyl acetate/CH2Cl2) to afford (S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (2.17 g, 73.1%) as a white solid. LC-MS retention time 0.930 min; Calcd. for C12H181N3O2363.04 Found m/z 364.06 [M+H]+. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 3 min, a hold time of 1 min and an analysis time of 4 min where Solvent A was 10% acetonitrile/90% water/0.1% TFA and Solvent B was 90% acetonitrile/10% water/0.1% TFA. 1H NMR (500 MHz, MeOD) δ ppm 7.52-7.64 (m, 1H), 4.95-5.10 (m, 1H), 3.57-3.70 (m, 1H), 3.47-3.57 (m, 1H), 2.37-2.55 (m, 1H), 1.94-2.10 (m, 3H), 1.46 (s, 4H), 1.27 (s, 5H).

후처리

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted several times with ethyl acetate
  3. dry with materialThe combined organic phases were dried (brine, Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a flash chromatography (sample was dry loaded on silica gel and eluted with, 0 to 40% ethyl acetate/CH2Cl2)

출처 및 근거

ORD 기록
ord-c9945aca32454ecfb5532f5e53dd22ce
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006455B2

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