Iodine → HCID 59382830, compound

HRID 2355391Notes

Reaction equation

HRID 2355391 reaction equation
[Mg].II.Cl[CH2:5][CH2:6][CH2:7][CH2:8][O:9][CH3:10].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](=[O:38])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[Cl:37])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]>C1COCC1>[Cl:37][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[C@:24]([C@@H:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])[CH2:19]1)([OH:38])[CH2:5][CH2:6][CH2:7][CH2:8][O:9][CH3:10]

Participants

6

Reactant 4

HCID 807IodineHCID 873631-Chloro-4-methoxybutaneHCID 5462224Magnesium2×HCID 59382868HCID 59382868, compound

Product 1

HCID 59382830HCID 59382830, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 250-mL three-necked flask was charged with magnesium turning (2.88 g, 0.12 mol) and a small crystal of iodine. The flask was evacuated and refilled with N2. A solution of 1-chloro-4-methoxybutane (15 g, 0.12 mol) in THF (60 mL) was added dropwise to the above mixture. After heating under reflux for 2 h most of magnesium had been consumed and the Grignard solution was cooled to rt. A 250-mL three-necked flask was charged with (3R)-1-(tert-butoxycarbonyl)-3-((2-(2-chlorophenyl))benzoyl)piperidine (4.43 g, 11 mmol) and THF (50 ml), evacuated and refilled with N2. The mixture was cooled in a dry ice-acetone bath and the Grignard reagent was added dropwise. The mixture was allowed to warm slowly to rt and stirred overnight. The mixture was quenched with sat'd aq NH4Cl (100 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated to give the crude product which was purified by flash column chromatography to afford pure (3R)-tert-butyl 3-((S)-1-(2-(2-chlorophenyl)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate (2.5 g, 47%).

Workup

  1. customThe flask was evacuated
  2. additionrefilled with N2
  3. temperatureAfter heating
  4. customhad been consumed
  5. customevacuated
  6. additionrefilled with N2
  7. temperatureThe mixture was cooled in a dry ice-acetone bath
  8. additionthe Grignard reagent was added dropwise
  9. temperatureto warm slowly to rt
  10. customThe mixture was quenched with sat'd aq NH4Cl (100 mL)
  11. extractionextracted with EtOAc
  12. dry with materialThe combined organic layers were dried over Na2SO4
  13. concentrationconcentrated
  14. customto give the crude product which
  15. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-be9cf628ef104613bd4b768a5fb5bff9
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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