Sodium hydride → HCID 54140711, compound

HRID 1374666Notes

Reaction equation

HRID 1374666 reaction equation
[H-].[Na+].[OH:3][CH2:4][C@H:5]([NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:6]([OH:8])=[O:7].Br[CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH:19]1([CH2:18][O:3][CH2:4][C@H:5]([NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:6]([OH:8])=[O:7])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 137636Cyclohexane, (bromomethyl)-3×

Product 1

HCID 54140711HCID 54140711, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Undercooling with ice, sodium hydride (60%, 3.95 g) was added to a solution of (2S)-3-hydroxy-2-t-butoxycarbonylaminopropanoic acid (10.11 g) in dimethylformamide (200 ml, hereinafter abbreviated as DMF). The mixture was stirred for 30 minutes at 0° C. Under cooling with ice, (bromomethyl)cyclohexane (9.0 ml) was added dropwise to the reaction mixture and tetrabutylammonium iodide (910 mg) was added thereto. The mixture was stirred for 23 hours at room temperature. Further, (bromomethyl)cyclohexane (2.1 ml) was added dropwise to the reaction mixture. The mixture was stirred for 4 hours. (Bromomethyl)cyclohexane (2.1 ml) was added dropwise to reaciton mixture again. The mixture was stirred for 25 hours at room temperature. The reaction mixture was concentrated and the residue was diluted with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and saturated aqueous sodium chloride, successively, dried over anhydrous magnesium sulfate. The organic layer was concentrated and the residue was purified by silica gel column chromatography (chloroform:methanol=97:3) to give the title compound (2.52 g) having the following physical data.

Workup

  1. additionwas added
  2. stirringThe mixture was stirred for 23 hours at room temperature
  3. stirringThe mixture was stirred for 4 hours
  4. stirringThe mixture was stirred for 25 hours at room temperature
  5. concentrationThe reaction mixture was concentrated
  6. additionthe residue was diluted with 1N hydrochloric acid
  7. extractionextracted with ethyl acetate
  8. washThe extract was washed with water and saturated aqueous sodium chloride
  9. dry with materialsuccessively, dried over anhydrous magnesium sulfate
  10. concentrationThe organic layer was concentrated
  11. customthe residue was purified by silica gel column chromatography (chloroform:methanol=97:3)

Sources & evidence

ORD record
ord-fa9d63408a14483b86ce82b26bd2fbf0
Source dataset
uspto-grants-2007_01
Patent number
US07166590B2

Reaction notes

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