Benzyl Bromide → HCID 178461669, compound

HRID 541110Notes

Reaction equation

HRID 541110 reaction equation
[OH:1][C@H:2]([C@@H:8]([OH:20])[CH:9]1[CH2:11][N@@:10]1[C@@H:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])[C:3]([O:5][CH2:6][CH3:7])=O.[Li+].[Cl-].[BH4-].[Na+].[H-].[Na+].[CH:27]1[CH:32]=[CH:31][C:30]([CH2:33]Br)=[CH:29][CH:28]=1>CCO.CN(C=O)C.C(OCC)(=O)C>[C:14]1([C@H:12]([N@:10]2[CH2:11][CH:9]2[C@H:8]([O:20][CH2:12][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:2]([O:1][CH2:33][C:30]2[CH:31]=[CH:32][CH:27]=[CH:28][CH:29]=2)[CH2:3][O:5][CH2:6][C:7]2[CH:3]=[CH:2][CH:8]=[CH:9][CH:11]=2)[CH3:13])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

9

Reactant 5

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 433294Lithium ChlorideHCID 4311764Sodium borohydrideHCID 178472579HCID 178472579, compound

Product 1

HCID 178461669HCID 178461669, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2R,3S)-ethyl 2,3-dihydroxy-3-((R)-1-((R)-1-phenylethyl)aziridin-2-yl)propanoate (1 g, 3.57 mmol) in EtOH was added LiCl (756 mg, 17.85 mmol, 5 equiv) and NaBH4 (680 mg, 17.85 mmol, 5 equiv) at 0° C. The reaction mixture was stirred for 20 hrs at 0° C. and quenched with water. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over MgSO4, filtered through a pad of celite and concentrated in vacuo. The resulting alcohol was used without further purification. To a slurry of NaH (471 mg, 11.78 mmol, 60% dispersion in mineral oil, 3.3 equiv) in DMF (6 mL, 2 M) was added a solution of the resulting alcohol in DMF (7 mL, 0.5 M) at 0° C. After 30 min, BnBr (1.4 mL, 11.78 mmol, 3.3 equiv) was added. The reaction mixture was stirred for 6 hrs at room temperature, diluted with ethyl acetate and quenched with water. The mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The resulting crude product was purified by silica gel flash chromatography with ethyl acetate/hexane (1/9 to 1/6) to afford the title product. Yield: 1.29 g (71% over 2 steps); yellow oil.

Workup

  1. customquenched with water
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. filtrationfiltered through a pad of celite
  6. concentrationconcentrated in vacuo
  7. customThe resulting alcohol was used without further purification
  8. waitAfter 30 min
  9. stirringThe reaction mixture was stirred for 6 hrs at room temperature
  10. customquenched with water
  11. extractionThe mixture was extracted with ethyl acetate
  12. washThe combined organic layer was washed with brine
  13. dry with materialdried over anhydrous MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe resulting crude product was purified by silica gel flash chromatography with ethyl acetate/hexane (1/9 to 1/6)

Sources & evidence

ORD record
ord-343464aa73ed475f86fcc5fa862634f9
Source dataset
uspto-grants-2014_10
Patent number
US08871950B1

Reaction notes

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