1,3-Dibromopropane → HCID 68680811, compound

HRID 1454567Notes

Reaction equation

HRID 1454567 reaction equation
[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]

Participants

10

Reactant 5

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

Product 1

HCID 68680811HCID 68680811, compoundYield 9.8%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

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).

Workup

  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))

Sources & evidence

ORD record
ord-edbbd9d1b41b471fa8501f0b833843c6
Source dataset
uspto-grants-2009_01
Patent number
US07479562B2

Reaction notes

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