p-Toluenesulfonic acid → HCID 14140251, compound

HRID 979181Notes

Reaction equation

HRID 979181 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C@H:4]([CH3:16])[NH:5][C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7].[H-].[CH2:19]([Al+]CC(C)C)C(C)C.COC(OC)OC.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][CH:3]([O:17][CH3:19])[C@H:4]([CH3:16])[NH:5][C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 6993447Z-Ala-OMeHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 14140251HCID 14140251, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of N-carbobenzyloxy-L-alanine methyl ester (41.0 g, 0.71 mol) in 300 ml anhydrous toluene at -78° C., under N2, was added dropwise a toluene solution of diisobutyl-aluminum hydride (25% wt. % soln., 234 ml, 0.345 mol) over 0.5 hour. After the addition was complete the mixture was stirred 0.75 hour and quenched with the dropwise addition of 2N HCl (350 ml). The solution was warmed to room temperature and extracted with ethyl acetate. The combined organic layers were washed with brine and dried (MgSO4) and concentrated in vacuo. The residue was dissolved in 400 ml methanol and trimethylorthoformate (43 ml, 0.40 mol) and p-toluenesulfonic acid (0.723 g 3.8 mmol) was added. The mixture was stirred overnight and concentrated in vacuo to approximately 70% of the original volume. The residue was poured onto 800 ml of saturated NaHCO3. Ether and water were added. The aqueous layer was extracted with ether. The combined organic layers were washed with brine and dried (MgSO4) and concentrated in vacuo. Chromatography of the residue on HPLC using 30% ethyl acetate in hexanes as eluents provided the oily product N-carbobenzyloxy-L-alaninal dimethyl acetal.

Workup

  1. additionAfter the addition
  2. customquenched with the dropwise addition of 2N HCl (350 ml)
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in 400 ml methanol
  8. stirringThe mixture was stirred overnight
  9. concentrationconcentrated in vacuo to approximately 70% of the original volume
  10. additionThe residue was poured onto 800 ml of saturated NaHCO3
  11. additionEther and water were added
  12. extractionThe aqueous layer was extracted with ether
  13. washThe combined organic layers were washed with brine
  14. dry with materialdried (MgSO4)
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-014d1790d6454836bf56ab177836c221
Source dataset
uspto-grants-1987_05
Patent number
US04666906

Reaction notes

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