Diethyl Malonate → Diethyl 3-(benzyloxy)cyclobutane-1,1-dicarboxylate

HRID 2393930Notes

Reaction equation

HRID 2393930 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[CH2:15][CH:16]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:17]Br>O1CCOCC1>[CH2:20]([O:19][CH:16]1[CH2:17][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])([C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH2:15]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydride2×HCID 3468282{[(1-Bromo-3-chloropropan-2-yl)oxy]methyl}benzene

Product 1

HCID 12815110Diethyl 3-(benzyloxy)cyclobutane-1,1-dicarboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred slurry of 4.6 g (0.19 mol) sodium hydride in 115 mL of dry dioxane was added dropwise 30.4 (0.10 mol) of diethyl malonate over a 30 min period. After this addition was complete, 50.0 g (0.19 mol) of 1-chloro-2-benzyloxy-3-bromopropane 3 was added dropwise in 30 min (Step 2). The mixture was heated at reflux for 44 hr, cooled to room temperature, and 4.6 g (0.19 mol) of sodium hydride in 50 mL of dioxane was added in portions. The mixture was heated at reflux for an additional 120 hr. The solvent was partially removed under reduced pressure and the mixture was treated with 100 mL of water. The organic layer was extracted into ether. The ether extracts were dried and concentrated and the residue was distilled under reduced pressure. Distillation through a 12-in Vigreux column yielded 49.0 g (85%) of diethyl 3-benzyloxycyclobutane-1,1-dicarboxylate 4 bp 174°-176° C. (0.9 mm); 1H NMR(CDCl3) δ 1.23 (t, J=7 Hz, 6H, CH3), 4.0-4.7 (m, 1H OCH), 4.34 (s, 2H OCH2), 4.13 (q, J=7 Hz, 4H, OCOCH2), 7.23 (s, 5H, phenyl).

Workup

  1. additionAfter this addition
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 44 hr
  4. temperatureThe mixture was heated
  5. temperatureat reflux for an additional 120 hr
  6. customThe solvent was partially removed under reduced pressure
  7. additionthe mixture was treated with 100 mL of water
  8. extractionThe organic layer was extracted into ether
  9. dry with materialThe ether extracts were dried
  10. concentrationconcentrated
  11. distillationthe residue was distilled under reduced pressure
  12. distillationDistillation through a 12-in Vigreux column

Sources & evidence

ORD record
ord-8198053285224fdf98e450361247f1f5
Source dataset
uspto-grants-1998_09
Patent number
US05808146

Reaction notes

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