Isobutanol → HCID 23434501, compound

HRID 2414760Notes

Reaction equation

HRID 2414760 reaction equation
[H-].[Na+].[CH2:3]([OH:7])[CH:4](C)[CH3:5].BrC[C:10](=[O:17])[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13].[CH2:18]1COCC1>CCCCCC>[CH2:15]([O:14][C:12](=[O:13])[CH2:11][C:10]([O:7][CH:3]([CH3:18])[CH2:4][CH3:5])=[O:17])[CH3:16]

Participants

6

Reactant 4

HCID 6560IsobutanolHCID 8028Tetrahydrofuran3×HCID 24758Sodium hydride2×HCID 575284Ethyl 4-bromo-3-oxobutanoate

Product 1

HCID 23434501HCID 23434501, compound

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent2×

Procedure

A sodium hydride dispersion in mineral oil, 160.0 grams (60%, 4.0 moles) was placed in a 12 L round bottom flask equipped with mechanical stirrer, thermometer, addition funnel and nitrogen inlet. The flask was cooled with an ice bath and 3.5 L of dry THF added with sting, while maintaining the temperature below 20° C. To the suspension of stirred sodium hydride was added 376.4 grams (4.0 moles) of iso-butanol dissolved in 0.3 L of THF. The addition was carried out over about 2 hrs. at such a rate so as to maintain the temperature below 10° C. The mixture was then allowed to warm to room temperature and stired for 1 hour. To the re-cooled solution, over the course of 1 hour, was added 418 grams (2.0 moles) of ethyl 4-bromoacetoacetate (A. Svendsen, and P. M. Boll, Tetrahedron 1973 29, 4251-4258) dissolved in 0.3 L of THF. The rate of addition was controlled so as to keep the temperature below 10° C. The ice bath was removed and the brown slurry stirred overnight at room temperature. The reaction was quenched by pouring into 2.2 L of 1.0 N hydrochloric acid and the phases separated. The aqueous phase was extracted with 0.5 L of diethyl ether; the combined organic phase washed with 1.0 L of saturated brine and dried over MgSO4. After filtering and removal of solvent 830 g of a red-brown oil was obtained. The product was dissolved in 0.4 L of hexane and applied to a column of 8.0 L of silica wet-packed in hexane. The column was eluted with 4.0 L of hexane; 8.0 L of 3:1 hexane to diethyl ether and 12.0 L of 2:1 hexane to diethyl ether. The second fraction, 459.3 gram, was reapplied to a column of 4.0 L of silica wet-packed in hexane. The column was eluted with 3.0 L of 95:5 hexane to diethyl ether; 2.0 L of 9:1 hexane to diethyl ether; 2.0 L of 4:1 hexane to diethyl ether and 12.0 L of 3:1 hexane to diethyl ether. The major fraction was bulb-to-bulb distilled using a Kugelrohr apparatus and an oven temperature of 40-45° C. at <1.0 torr. The desired product was obtained as an oil, 145.9 gram (33%).

Workup

  1. customequipped with mechanical stirrer
  2. additionthermometer, addition funnel and nitrogen inlet
  3. temperatureThe flask was cooled with an ice bath
  4. temperaturewhile maintaining the temperature below 20° C
  5. additionThe addition
  6. temperatureat such a rate so as to maintain the temperature below 10° C
  7. waitstired for 1 hour
  8. additionThe rate of addition
  9. customthe temperature below 10° C
  10. customThe ice bath was removed
  11. customThe reaction was quenched
  12. additionby pouring into 2.2 L of 1.0 N hydrochloric acid
  13. customthe phases separated
  14. extractionThe aqueous phase was extracted with 0.5 L of diethyl ether
  15. washthe combined organic phase washed with 1.0 L of saturated brine
  16. dry with materialdried over MgSO4
  17. filtrationAfter filtering
  18. customremoval of solvent 830 g of a red-brown oil
  19. customwas obtained
  20. washThe column was eluted with 4.0 L of hexane
  21. washThe column was eluted with 3.0 L of 95:5 hexane to diethyl ether
  22. distillationdistilled
  23. customa Kugelrohr apparatus and an oven temperature of 40-45° C.

Sources & evidence

ORD record
ord-61f4dc7d248a469f9ce18c139b896193
Source dataset
uspto-grants-2004_11
Patent number
US06815447B2

Reaction notes

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