Citric Acid → Cbz-L-Phenylalaninal

HRID 1603808Notes

Reaction equation

HRID 1603808 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH2:11]([O:18][C:19]([NH:21][C@H:22]([CH2:30][OH:31])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.CCOCC.C(N(CC)CC)C>[CH2:11]([O:18][C:19]([NH:21][C@H:22]([CH:30]=[O:31])[CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:20])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 311Citric Acid2×HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 853481N-carbobenzoxy-L-phenylalanilol

Product 1

HCID 7021150Cbz-L-PhenylalaninalYield 103.2%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1.8 ml of dimethyl sulfoxide in 20 ml of dichloromethane cooled to -78° C. was added slowly 1.65 ml of oxalyl chloride. The solution was stirred for 10 min at -78° C. and a solution of 3.6 g (0.012 mol) of N-((benzyloxy)carbonyl)-L-phenylalaninol in 45 ml of dichloromethane was added slowly. The resulting solution was stirred at -78° C. for 15 min, then 1 min at 0° C., recooling to -78° C. and 7.6 ml of triethylamine was added over 10 min. After stirring at -78° C. for 25 min, 20 ml of cold 10% aq. citric acid solution was added. After warming to 0° C., 200 ml of ether and 55 ml of cold 10% citric acid added. The organic layer was separated by separatory funnel and washed repeatedly (5×60 ml) with water and finally with satd. NaCl solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo at RT to give 3.51 g of the desired compound as an off-white solid.

Workup

  1. stirringThe resulting solution was stirred at -78° C. for 15 min
  2. custom1 min
  3. customat 0° C.
  4. customrecooling to -78° C.
  5. stirringAfter stirring at -78° C. for 25 min
  6. temperatureAfter warming to 0° C.
  7. customThe organic layer was separated by separatory funnel
  8. washwashed repeatedly (5×60 ml) with water
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo at RT

Sources & evidence

ORD record
ord-8997e34bf5c7415bb41637749b330c5d
Source dataset
uspto-grants-1999_11
Patent number
US05990135

Reaction notes

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