Hydrochloric Acid → HCID 14651684, compound

HRID 346301Notes

Reaction equation

HRID 346301 reaction equation
C([CH:3]([C:7](Cl)=[O:8])[C:4](Cl)=[O:5])C.Cl.[CH3:11][O:12][C:13](=[O:20])[C@H:14]([CH2:16][CH:17]([CH3:19])[CH3:18])[NH2:15].C(N([CH2:26][CH3:27])CC)C.Cl.[OH2:29]>ClCCl>[CH2:26]([O:29][C:7](=[O:8])[CH2:3][C:4]([NH:15][C@@H:14]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:13]([O:12][CH3:11])=[O:20])=[O:5])[CH3:27]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 8471TriethylamineHCID 2723695Leucine methyl ester hydrochlorideHCID 109209242-Ethylpropanedioyl dichloride

Product 1

HCID 14651684HCID 14651684, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 60 g (0.4 mol) of ethyl malonyl chloride in 150 ml of dichloromethane is added over 0.5 hours to a cold (10° C.) solution of 72.76 g (0.4 mol) of L-leucine methyl ester hydrochloride and 86.02 g (0.85 mol) of triethylamine in 1.5 L of dichloromethane with stirring and keeping the temperature at 10° C. during the addition. The solution is allowed to warm to room temperature, stirred another 0.5 hours and poured into 500 ml of water plus ice chips and 80 ml of 1N hydrochloric acid solution. The organic layer is separated and washed successively with 500 ml of cold water, 500 ml of a 2% aqueous solution of sodium bicarbonate and 500 ml of water. The organic layer is separated, dried over magnesium sulfate, charcoaled and filtered. The filtrate is concentrated to afford 101.8 g of (S)-2-[(3-ethoxy-1,3-dioxopropyl)amino]-4-methylpentanoic acid, methyl ester as a viscous oil. Thin layer chromatography (TLC) (ethyl acetate, silica gel, iodine) Rf =0.75. This material is used directly in the next ring closure step.

Workup

  1. customat 10° C.
  2. additionduring the addition
  3. stirringstirred another 0.5 hours
  4. customThe organic layer is separated
  5. washwashed successively with 500 ml of cold water, 500 ml of a 2% aqueous solution of sodium bicarbonate and 500 ml of water
  6. customThe organic layer is separated
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated

Sources & evidence

ORD record
ord-afbf2963526d49a5bf7b8ce8d92119b0
Source dataset
uspto-grants-1991_10
Patent number
US05061808

Reaction notes

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