1,3-Dibromopropane → HCID 68680811、化合物

HRID 1454567ノート

反応式

HRID 1454567 の反応式
[Si]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[CH2:16][CH2:15][NH:14][C:13]1=[O:17])(C(C)(C)C)(C)C.[H-].[Na+].Br[CH2:21][CH2:22][CH2:23]Br.CCN(C(C)C)C(C)C.[NH:34]1[CH2:39][CH2:38][CH:37]([O:40][C:41](=[O:55])[NH:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH2:36][CH2:35]1>CN(C=O)C.Cl.C(Cl)Cl.C(#N)C>[OH:8][CH2:9][CH2:10][CH2:11][N:12]1[CH2:16][CH2:15][N:14]([CH2:21][CH2:22][CH2:23][N:34]2[CH2:35][CH2:36][CH:37]([O:40][C:41](=[O:55])[NH:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH2:38][CH2:39]2)[C:13]1=[O:17]

参加物

10

反応物 5

HCID 80011,3-DibromopropaneHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 10851461Biphenyl-2-ylcarbamic Acid Piperidin-4-yl EsterHCID 57530581HCID 57530581、化合物

生成物 1

HCID 68680811HCID 68680811、化合物収率 9.8%

試薬・触媒・溶媒 4

HCID 313Hydrochloric Acid溶媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
50 °C

実験手順

To a stirred solution of 1-[3-(tert-butyldimethylsilanyloxy)propyl]imidazolidin-2-one (38 g, 147 mmol; prepared as described in Preparation 5) in DMF (500 mL) was added NaH (6.4 g, 60% in mineral oil, 160 mmol). The reaction was then heated to 50° C. and was allowed to stir until bubbling of H2 ceased (˜1 hours). The reaction was then cooled to room temperature. To the reaction mixture was dropwise added 1,3-dibromopropane (14.0 mL, 147 mmol). The reaction was allowed to stir at room temperature for 16 hours. Next, DIPEA (52 mL, 294 mmol) and biphenyl-2-ylcarbamic acid piperidin-4-yl ester (47 g, 160 mmol; prepared as described in Preparation 3) was added to the reaction and this was heated to 50° C. for 18 hours. After 18 hours, the reaction was cooled to room temperature and then condensed under reduced pressure. The crude reaction mixture was dissolved in 1:1 mixture of 1N HCl:ACN (250 mL) and heated to 50° C. for 5 hours. The reaction was then condensed under reduced pressure, dissolved in DCM (500 mL), washed with 1N HCl (500 mL), water (500 mL), NaCl (sat.) (500 mL), dried over MgSO4 and then filtered. The solvent was removed under reduced pressure. The crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq)) to afford the title compound in 9.8% yield (8.6 g, 14.4 mmol).

後処理

  1. customuntil bubbling of H2
  2. custom(˜1 hours)
  3. temperatureThe reaction was then cooled to room temperature
  4. stirringto stir at room temperature for 16 hours
  5. temperaturethis was heated to 50° C. for 18 hours
  6. temperaturethe reaction was cooled to room temperature
  7. customcondensed under reduced pressure
  8. customThe crude reaction mixture
  9. customcondensed under reduced pressure
  10. washwashed with 1N HCl (500 mL), water (500 mL), NaCl (sat.) (500 mL)
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customThe solvent was removed under reduced pressure
  14. customThe crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq))

出典と根拠

ORDレコード
ord-edbbd9d1b41b471fa8501f0b833843c6
出典データセット
uspto-grants-2009_01
特許番号
US07479562B2

反応ノート

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