Iodine → HCID 131729008, compound

HRID 1010900Notes

Reaction equation

HRID 1010900 reaction equation
[Mg].BrCC.II.Cl[CH:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1.[C:15]([O:19][C:20](=[O:32])[NH:21][C@H:22]([C:24]1[CH:29]=[CH:28][C:27]([CH:30]=[O:31])=[CH:26][CH:25]=1)[CH3:23])([CH3:18])([CH3:17])[CH3:16].[Cl-].[NH4+]>O1CCCC1>[C:15]([O:19][C:20](=[O:32])[NH:21][C@H:22]([C:24]1[CH:25]=[CH:26][C:27]([CH:30]([OH:31])[CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:28][CH:29]=1)[CH3:23])([CH3:16])([CH3:17])[CH3:18]

Participants

8

Reactant 6

HCID 807Iodine2×HCID 6332Ethyl BromideHCID 25517Ammonium ChlorideHCID 793424-chloro-N-methylpiperidineHCID 5462224MagnesiumHCID 89479126HCID 89479126, compound

Product 1

HCID 131729008HCID 131729008, compoundYield 81.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a mixture of 975 mg of magnesium, 100 μL of bromoethane, and 20 μL of tetrahydrofuran, a catalyst amount of iodine was added, and the mixture was stirred for about 10 minutes until the brown color from iodine disappears. Thereto, 20 mL of a tetrahydrofuran solution containing 5.9 g of 4-chloro-1-methylpiperidine was added, and heated for 2.5 hours under reflux. Thus produced white suspension was cooled to 0° C., and 10 mL of a tetrahydrofuran solution containing 2 g of the compound [15-1] was added thereto. After the overnight stirring under gradually heating back to room temperature, a saturated aqueous solution of ammonium chloride was added thereto, and extracted with ethyl acetate. The obtained organic layer was washed with water and saturated brine in that order, and dried over anhydrous magnesium sulfate. The insolubles were filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=100/0-90/10), to obtain 2.27 g of tert-butyl((1S)-1-{4-[hydroxy(1-methylpiperidin-4-yl)methyl]phenyl}ethyl)carbamate [23-1] (hereinafter, referred to as the compound [23-1]).

Workup

  1. additionwas added
  2. temperatureheated for 2.5 hours
  3. temperatureunder reflux
  4. additionwas added
  5. temperatureunder gradually heating back to room temperature
  6. extractionextracted with ethyl acetate
  7. washThe obtained organic layer was washed with water and saturated brine in that order
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe insolubles were filtered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customthe resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=100/0-90/10)

Sources & evidence

ORD record
ord-c6f2670a733947198f633d52a82fc2c8
Source dataset
uspto-grants-2011_07
Patent number
US07977336B2

Reaction notes

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