Ethyl diazoacetate → HCID 11471183, compound

HRID 1183197Notes

Reaction equation

HRID 1183197 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[CH2:7])=[CH:4][CH:3]=1.[N+](=[CH:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N-]>CC(OC)(C)C>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([C@H:6]2[CH2:7][C@@H:12]2[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 12192Ethyl diazoacetateHCID 162634-Bromostyrene

Product 1

HCID 11471183HCID 11471183, compoundYield 88.4%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent3×

Procedure

To a 1-neck, 1-L round bottom flask equipped with a magnetic stirrer was added 265 mL methyl tert-butyl ether. The flask was evacuated and flushed with nitrogen three times. 2,2′-Isopropylidenebis[(4R)-4-tert-butyl-2-oxazolidine] (2.39 g, 8.03 mmol) was added, followed by copper(I) tridluoromethanesulfonate benzene complex (4.49 g, 8.03 mmol). The green suspension was stirred at room temperature for about 2 hours and was then filtered. The filtrate was added to a 4-neck, 5-L, round bottom flask equipped with a mechanical stirrer, thermocouple, nitrogen bubbler, and addition funnel. Then, 4-bromostyrene (150 g, 0.803 mol) was added to this solution and the reaction was cooled to 0° C. via an ice/water bath. Ethyl diazoacetate (167 mL, 1.606 mol) was dissolved in 1675 mL of MTBE and the solution was evacuated/flushed with nitrogen three times. This solution was then added to an addition funnel and added dropwise to the reaction mixture. A slight exotherm was observed. The ethyl diazoacetate was allowed to add slowly over the weekend and the reaction slowly warmed to room temperature. The reaction was poured into a large extractor and diluted with 4 L MTBE. The organics were washed with 2×1 L 3% aq. ammonium hydroxide and 2 L brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was dissolved in heptane and a small amount of dichloromethane, injected onto an ISCO 1500 g column prepacked in heptane. The column was eluted with 100% heptane over 1 column volume, 0-20% ethyl acetate/heptane over 6.5 column volumes, and held at 20% ethyl acetate/heptane over 8 column volumes. The product containing fractions were collected and concentrated to give 191 g (yield 88%) of the title compound. 1H NMR (500 MHz, (CDCl3): 7.42 (d, 2H), 7.01 (d, 2H), 4.21 (q, 2H), 2.49 (m, 1H), 1.88 (m, 1H), 1.62 (m, 2H), 1.25 (t, 3H).

Workup

  1. customThe flask was evacuated
  2. customflushed with nitrogen three times
  3. filtrationwas then filtered
  4. additionThe filtrate was added to a 4-neck, 5-L, round bottom flask
  5. customequipped with a mechanical stirrer
  6. additionthermocouple, nitrogen bubbler, and addition funnel
  7. temperaturethe reaction was cooled to 0° C. via an ice/water bath
  8. customthe solution was evacuated/flushed with nitrogen three times
  9. additionThis solution was then added to an addition funnel
  10. additionadded dropwise to the reaction mixture
  11. additionto add slowly over the weekend
  12. customthe reaction
  13. temperatureslowly warmed to room temperature
  14. additionThe reaction was poured into a large extractor
  15. washThe organics were washed with 2×1 L 3% aq. ammonium hydroxide and 2 L brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated
  19. dissolutionThe residue was dissolved in heptane
  20. washThe column was eluted with 100% heptane over 1 column volume, 0-20% ethyl acetate/heptane over 6.5 column volumes
  21. additionThe product containing fractions
  22. customwere collected
  23. concentrationconcentrated

Sources & evidence

ORD record
ord-8cde185f2664419fac643c7c986c10b9
Source dataset
uspto-grants-2014_03
Patent number
US08664253B2

Reaction notes

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