Nitrogen → Ethyl 2-hydroxypent-4-ynoate

HRID 1424308Notes

Reaction equation

HRID 1424308 reaction equation
N#N.[C:3]1(C)[CH:8]=CC=C[CH:4]=1.[C:10]([O:14][CH2:15][CH3:16])(=[O:13])[CH:11]=[O:12].C(Br)C#C>C1COCC1.CCOCC.[Zn].C(Br)C#C>[CH2:15]([O:14][C:10](=[O:13])[CH:11]([OH:12])[CH2:8][C:3]#[CH:4])[CH3:16]

Participants

9

Reactant 4

HCID 947NitrogenHCID 1140Toluene2×HCID 7842Propargyl bromideHCID 70211Ethyl oxoacetate

Product 1

HCID 14640100Ethyl 2-hydroxypent-4-ynoateYield 51%

Reagents, catalysts & solvents 4

HCID 7842Propargyl bromideCatalystHCID 23994ZincCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Propargyl bromide (˜10 g) was added under a blanket of N2 to a 3-L round bottom flask containing 350 mL anhydrous THF and Zn (230 g, 3.5 mol). The mixture was stirred at room temperature for 30 min and then cooled in an ice bath. A toluene solution of ethyl glyoxylate (51 wt %, determined by NMR, 473 g, 2.36 mol) and a toluene solution of propargyl bromide (80 wt %, 352 g, 2.36 mol) were combined in 500 mL dry THF and 700 mL dry ether. This mixture was then added dropwise to the stirred slurry. After the addition was complete, the mixture was stirred at 0° C. overnight. The reaction mixture was then poured into a 4-L Erlenmeyer flask containing 1 L of ice-cold 3M HCl. After separation of the organic layer, the aqueous layer was extracted with ether (3×300 mL) and the combined organic layers were dried over MgSO4. Filtration and removal of the solvents by rotary evaporation gave a dark blue oil, which was purified by column chromatography using silica gel with EtOAc/hexanes (30/70) as the eluent. Vacuum distillation of the resulting material (50-55° C./100 mTorr) gave the ester 2 as a colorless oil (170 g, 51%). 1H NMR δ 4.25 (m, 3H), 3.11 (d, 1H, J=6.4 Hz), 2.65 (m, 2H), 2.03 (t, 1H, J=2.7 Hz), 1.28 (t, 3H, J=7.2 Hz). 13C NMR δ 172.99, 78.53, 71.25, 68.64, 62.11, 24.81, 14.13.

Workup

  1. temperaturecooled in an ice bath
  2. additionThis mixture was then added dropwise to the stirred slurry
  3. additionAfter the addition
  4. stirringthe mixture was stirred at 0° C. overnight
  5. additionThe reaction mixture was then poured into a 4-L Erlenmeyer flask
  6. customAfter separation of the organic layer
  7. extractionthe aqueous layer was extracted with ether (3×300 mL)
  8. dry with materialthe combined organic layers were dried over MgSO4
  9. filtrationFiltration and removal of the solvents
  10. customby rotary evaporation
  11. customgave a dark blue oil, which
  12. customwas purified by column chromatography
  13. distillationVacuum distillation of the resulting material (50-55° C./100 mTorr)

Sources & evidence

ORD record
ord-0f612f626088426d8a670cbac03497e1
Source dataset
uspto-grants-2015_01
Patent number
US08927682B2

Reaction notes

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