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

HRID 1708507Notes

Reaction equation

HRID 1708507 reaction equation
[CH2:1]([O:3][C:4](=[O:11])[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[H-].[Na+].Br[CH2:15][CH:16]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:17]Cl>O1CCOCC1>[CH2:20]([O:19][CH:16]1[CH2:17][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])([C:4]([O:3][CH2:1][CH3:2])=[O:11])[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-dicarboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Compound 1 was prepared according to the literature procedures of Avram, M., Nenitzescu, C. D. and Maxim, C. D. (1957) Chem. Ber., 90:1424 and Safanda, J. and Sobotka, P. (1982) Collect. Czech. Chem. Commun. 47:2440 with minor improvements. Malonic acid diethyl ester (258.6 ml, 1.703 moles) was added neat over a two hours period to a suspension of sodium hydride (51.10 g, 1.703 moles, Fluka N° 71614: 80% NaH in oil) in dioxane (1000 ml). This solution was stirred 90 min at room temperature. 1-Bromo-2-benzyloxy-3-chloro-propane (500 g, 1.789 moles) was added neat over a one hour period. The mixture was stirred for one hour at room temperature, followed by 24 hours at 125° C. After slow cooling to room temperature, a like quantity of sodium hydride was added neat in 5 g portions over one hour. The suspension was slowly heated to 125° C. and mechanically stirred for 120 hours at this temperature. The workup was as described in the literature references. Thus, compound 1 was first purified by distillation 172° C. at 0.6 Torr, followed by flash chromatography (tertiobutylmethylether/hexane=1/99 to 2/8) to afford 1: 382.5 g, 73.3% as a colourless oil.

Workup

  1. custom(1982) Collect
  2. stirringThe mixture was stirred for one hour at room temperature
  3. waitfollowed by 24 hours at 125° C
  4. temperatureAfter slow cooling to room temperature
  5. temperatureThe suspension was slowly heated to 125° C.
  6. stirringmechanically stirred for 120 hours at this temperature
  7. distillationThus, compound 1 was first purified by distillation 172° C. at 0.6 Torr
  8. customto afford 1

Sources & evidence

ORD record
ord-fc3c21ea60c54b4081d0695c9b7d9a91
Source dataset
uspto-grants-1994_10
Patent number
US05359044

Reaction notes

Loading…