Hydrochloric Acid → Ethyl 8-benzyloxycarbonylamino-3-ketooctanoate

HRID 703378Notes

Reaction equation

HRID 703378 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:32]([O:38][CH2:39][CH3:40])(=[O:37])[CH2:33]C([O-])=O.Cl>O1CCCC1>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17](=[O:19])[CH2:33][C:32]([O:38][CH2:39][CH3:40])=[O:37])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 747586-(((Phenylmethoxy)carbonyl)amino)hexanoic acidHCID 3595298Propanedioic acid, monoethyl ester

Product 1

HCID 10871380Ethyl 8-benzyloxycarbonylamino-3-ketooctanoateYield 70.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2.65 g (10 mmoles) of 6-benzyloxycarbonylaminohexanoic acid and 1.62 g (10 mmoles) of commercial 1,1'-carbonyldiimidazole in 25 ml of anhydrous tetrahydrofuran was stirred for 15 minutes at room temperature. To the reaction mixture was added a suspension of 6.18 g (40 mmoles) of a white powder of magnesium enolate of monoethyl malonate (prepared from 5.28 g of monoethyl malonate and 972 mg of magnesium) in 50 ml of anhydrous tetrahydrofuran. The mixture was stirred for 2 hours at room temperature. After addition of 50 ml of 1N hydrochloric acid and stirring for 10 minutes, the reaction mixture was extracted 3 times with 50 ml of chloroform. The chloroform layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated saline, then dried over anhydrous sodium sulfate and freed from the solvent by distillation. The residue was passed through a column of 100 g "Silica Gel 60" (Merck & Co.) and eluted with chloroform (20 g fraction size). Fractions No. 43 to No. 105 were combined and evaporated to dryness to yield 2.35 g (70% yield) of ethyl 8-benzyloxycarbonylamino-3-ketooctanoate.

Workup

  1. additionTo the reaction mixture was added
  2. stirringstirring for 10 minutes
  3. extractionthe reaction mixture was extracted 3 times with 50 ml of chloroform
  4. washThe chloroform layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated saline
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationfreed from the solvent by distillation
  7. washeluted with chloroform (20 g fraction size)
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-c42366d2cc6c4e73b42567fb8d1bf762
Source dataset
uspto-grants-1991_01
Patent number
US04983328

Reaction notes

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