2,2'-Bipyridine → 4,4-dimethyl-3-oxo-hex-5-enoic acid ethyl ester

HRID 887974Notes

Reaction equation

HRID 887974 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([OH:5])=O.N1C=CC=CC=1C1C=CC=CN=1.[Li]CCCC.[CH3:27][C:28](C)([CH:32]=[CH2:33])[C:29](Cl)=O>C1COCC1.CCOCC>[CH2:8]([O:7][C:1](=[O:6])[CH2:2][C:3](=[O:5])[C:28]([CH3:29])([CH3:27])[CH:32]=[CH2:33])[CH3:9]

Participants

7

Reactant 4

HCID 14742,2'-BipyridineHCID 70615Monoethyl malonateHCID 122516552,2-dimethyl-but-3-enoyl chlorideHCID 178418339Butyllithium2×

Product 1

HCID 107026324,4-dimethyl-3-oxo-hex-5-enoic acid ethyl esterYield 101.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Monoethyl hydrogen malonate (7.2 g, 0.05 mol) and bipyridyl (few milligrams) were dissolved in THF (90 ml) and the system was flushed with nitrogen. The solution was cooled to −70°, then BuLi (2.5 M in hexanes, 37 ml, 0.09 mol) was added. After the addition of only ˜10 ml of BuLi the solution turned pink and additional THF (15 ml) was required to enable magnetic stirring. The cooling bath was removed and the remaining BuLi was added, the temperature was allowed to reach −10°, upon which the solution turned colorless. The mixture was again cooled to −60° and a solution of 2,2-dimethyl-but-3-enoyl chloride (4.1 g, 0.03 mol) in THF (12 ml) was added dropwise. After addition was complete the mixture was allowed to warm to 0° and stir for 3 h, then it was added to a 1:1 mixture of ether/1M HCl (260 ml) at 0° and stirred for a further 1.5 h. The organic layer was removed, washed with HCl (1 M), sodium bicarbonate solution, brine then dried and evaporated to give 4,4-dimethyl-3-oxo-hex-5-enoic acid ethyl ester (5.6 g, 98%). (Hayashi et al., J. Org. Chem., 65:8402-8405 (2000). Distillation with a Kugelrohr oven (160°/1 mmHg) afforded pure material.

Workup

  1. customthe system was flushed with nitrogen
  2. temperatureThe solution was cooled to −70°
  3. customThe cooling bath was removed
  4. additionthe remaining BuLi was added
  5. customto reach −10°, upon which
  6. temperatureThe mixture was again cooled to −60°
  7. additionAfter addition
  8. temperatureto warm to 0°
  9. stirringstirred for a further 1.5 h
  10. customThe organic layer was removed
  11. washwashed with HCl (1 M), sodium bicarbonate solution, brine
  12. customthen dried
  13. customevaporated

Sources & evidence

ORD record
ord-94e9c050ab6c443cb0e0634ec97a1dfb
Source dataset
uspto-grants-2012_08
Patent number
US08247552B2

Reaction notes

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