Triethylamine → HCID 178445513, compound

HRID 1464355Notes

Reaction equation

HRID 1464355 reaction equation
C([NH:4][C@H:5]([PH:19]([OH:21])=[O:20])[C:6]([CH2:15][CH:16]([CH3:18])[CH3:17])(C(O)=O)[C:7]([O:9]CC)=[O:8])(=O)C.C(N(CC)CC)C>C1(C)C=CC=CC=1>[NH2:4][C@H:5]([PH:19]([OH:21])=[O:20])[CH:6]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:7]([OH:9])=[O:8]

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 178471404HCID 178471404, compound

Product 1

HCID 178445513HCID 178445513, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 13.47 g of ethyl hydrogen 2-[(R)-(acetamido)(hydroxyphosphinyl)methyl]-2(RS)-isobutylmalonate and 8.42 g of triethylamine in 420 ml of dry toluene was heated under reflux for 2 hours. After cooling, the solvent was removed by evaporation and the residue was dissolved in a mixture of 96 ml of water and 144 ml of concentrated hydrochloric acid and the solution was heated under reflux for 4 hours under a nitrogen atmosphere. The solution was evaporated to dryness and the 2-[(R)-(amino)(hydroxyphosphinyl)methyl]-4-methylvaleric acid obtained was dissolved in 225 ml of aqueous saturated sodium hydrogen carbonate solution and 45 ml of tetrahydrofuran. 30 g of solid sodium hydrogen carbonate and 45 ml of benzyl chloroformate were added and the mixture was stirred at room temperature for 48 hours in a nitrogen atmosphere. The solution was extracted twice with diethyl ether and the aqueous solution was acidified by the careful addition of hydrochloric acid and then extracted five times with dichloromethane containing 10% methanol. The extracts were dried over magnesium sulfate and evaporated to give a colorless gum which was crystallized from ethyl acetate. There were obtained 7.0 g of 2(R or S)-[(R)-benzyl-oxyformamido)(hydroxyphosphinyl)methyl]-4-methylvaleric acid as a single diasteroisomer in the form of a white solid; MS: 344 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 hours
  3. temperatureAfter cooling
  4. customthe solvent was removed by evaporation
  5. dissolutionthe residue was dissolved in a mixture of 96 ml of water and 144 ml of concentrated hydrochloric acid
  6. temperaturethe solution was heated
  7. temperatureunder reflux for 4 hours under a nitrogen atmosphere
  8. customThe solution was evaporated to dryness

Sources & evidence

ORD record
ord-ea8c1c29c507473690eddd7f52234eec
Source dataset
uspto-grants-1994_04
Patent number
US05304549

Reaction notes

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