Hydrochloric Acid → HCID 86684764, compound

HRID 2408326Notes

Reaction equation

HRID 2408326 reaction equation
[Mg+2].[Cl-].[Cl-].C(O)(=O)CC(O)=O.C([K])C.[C:14]([N:24]1[CH2:31][CH2:30][CH2:29][C@H:25]1[C:26]([OH:28])=O)([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15].C1N=CN(C(N2C=NC=C2)=O)C=1.[C:44]([O:50][CH2:51][CH3:52])(=[O:49])[CH2:45]C([O-])=O.Cl>C1COCC1>[CH2:51]([O:50][C:44](=[O:49])[CH2:45][C:26]([C@@H:25]1[CH2:29][CH2:30][CH2:31][N:24]1[C:14]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:15])=[O:28])[CH3:52]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 101987Benzyloxycarbonyl-L-prolineHCID 3595298Propanedioic acid, monoethyl esterHCID 5360315Magnesium ChlorideHCID 178461627HCID 178461627, compound

Product 1

HCID 86684764HCID 86684764, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
67.5 °C

Procedure

MgCl2 (153 g, 1640 mmol) was added in one portion to a solution of ethyl potassium malonate (354.9 g, 2085 mmol) in THF (2500 mL). The reaction mixture was stirred for 7 h at 65-70° C. and then at 30° C. overnight. A solution of Cbz-L-Proline (400 g) in THF (1000 mL) was slowly added to a mixture of CDI (312.1 g, 1924.8 mmol) in THF (1500 mL) and stirred at 30° C. for 2 h. The solution was added to the ethyl malonate mixture over 20 min at 20-30° C. and stirred overnight at 30° C. The mixture was cooled to 20° C. and neutralized with diluted HCl (4 N, 1800 mL). The solution was concentrated and the product was dissolved in ethyl acetate and rinsed with 5% aqueous sodium bicarbonate. The organic layer was concentrated and the residue was purified by flash column chromatography (eluent: petroleum ether:ethyl acetate=20:1 to 3:1) to give pure (S)-benzyl 2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate (460 g, 90% yield). Method A4 Rt: 1.23 min. m/z: 341.9 (M+Na)+ Exact mass: 319.1

Workup

  1. customat 30° C.
  2. customovernight
  3. stirringstirred at 30° C. for 2 h
  4. stirringstirred overnight at 30° C
  5. concentrationThe solution was concentrated
  6. dissolutionthe product was dissolved in ethyl acetate
  7. washrinsed with 5% aqueous sodium bicarbonate
  8. concentrationThe organic layer was concentrated
  9. customthe residue was purified by flash column chromatography (eluent: petroleum ether:ethyl acetate=20:1 to 3:1)

Sources & evidence

ORD record
ord-7254afcb375c427ea9f82d8b5f563654
Source dataset
uspto-grants-2014_08
Patent number
US08815849B2

Reaction notes

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