Diethyl Ether → ethyl (1R,2R)-2-(4-bromophenyl)cyclopropanecarboxylate

HRID 1711596Notes

Reaction equation

HRID 1711596 reaction equation
CC([O-:5])(C)C.[Na+].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:16]O2)=[CH:10][CH:9]=1.[CH3:17][CH2:18][O:19][CH2:20][CH3:21]>COCCOC.[NH4+].[Cl-].O>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([C@@H:14]2[CH2:16][C@H:17]2[C:18]([O:19][CH2:20][CH3:21])=[O:5])=[CH:12][CH:13]=1

Participants

7

Reactant 3

HCID 3283Diethyl EtherHCID 1194602-(4-Bromophenyl)oxiraneHCID 23676156Sodium t-butoxide

Product 1

HCID 66578655ethyl (1R,2R)-2-(4-bromophenyl)cyclopropanecarboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent2×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
70 °C

Procedure

NaOtBu (3.23 g, 33.6 mmol) and 10 mL of dry DME were charged in round bottom flask previously inerted with nitrogen. Triethyl phosphonoacetate (7.7 mL, 38.64 mmol) was added at a rate such to maintain internal temperature below 30° C., about 30 minutes. The mixture was stirred until complete dissolution was observed, about 30 minutes. A solution of chiral 2-(4-bromophenyl)oxirane Enantiomer 1 (Intermediate 9 Enantiomer 1) (3.35 g, 16.8 mmol) in 6 mL of dry DME was added dropwise maintaining internal temperature between 20° C. and 30° C. The reaction mixture was stirred at 60° C. for 24 h. The temperature was increased to 70° C. and maintained at this temperature for further 6 h. Mixture was cooled to room temperature, taken up with 100 mL Et2O, cooled to 0° C. and poured in approx. 80 mL cold ss NH4Cl. The solution was diluted with approx. 20 mL water, the phases were separated and the aqueous one extracted with Et2O 2×100 mL. Combined organics were dried over Na2SO4 and evaporated to dryness to get crude title material that was purified by SiO2 flash chromatography (Horizon 65M) eluting with Et2O/n-hexane 5/95 to get after evaporation of the solvent, pure title material, 3.35 g as a colourless oil.

Workup

  1. temperatureto maintain internal temperature below 30° C., about 30 minutes
  2. temperaturemaintaining internal temperature between 20° C. and 30° C
  3. stirringThe reaction mixture was stirred at 60° C. for 24 h
  4. temperaturemaintained at this temperature for further 6 h
  5. temperatureMixture was cooled to room temperature
  6. temperaturecooled to 0° C.
  7. customthe phases were separated
  8. extractionthe aqueous one extracted with Et2O 2×100 mL
  9. dry with materialCombined organics were dried over Na2SO4
  10. customevaporated to dryness
  11. customto get crude title material that
  12. customwas purified by SiO2 flash chromatography (Horizon 65M)
  13. washeluting with Et2O/n-hexane 5/95
  14. customto get
  15. customafter evaporation of the solvent, pure title material, 3.35 g as a colourless oil

Sources & evidence

ORD record
ord-1978c71ba0a54b8ca770e893e1949702
Source dataset
uspto-grants-2010_09
Patent number
US07790758B2

Reaction notes

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