Benzyl Alcohol → HCID 14420109, compound

HRID 2379645Notes

Reaction equation

HRID 2379645 reaction equation
[NH2:1][C@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4].[CH2:9](O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:40]1([O:46][C:47](Cl)=[O:48])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C1(C)C=CC=CC=1.C(OCC)C>[CH2:9]([O:7][C:6](=[O:8])[C@H:2]([CH:3]([CH3:5])[CH3:4])[NH:1][C:47]([O:46][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:48])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 5

HCID 244Benzyl AlcoholHCID 6101p-Toluenesulfonic acidHCID 6287L-Valine2×HCID 15891Phenyl chloroformateHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 14420109HCID 14420109, compoundYield 83.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

A slurry of 117.15 g (1 mol) of L-valine, 216.3 g (2.0 mol) of benzyl alcohol and 190.22 g (1.02 mol) of p-toluenesulfonic acid monohydrate in 450 mL of toluene was stirred and heated to reflux in an apparatus fitted with a Dean-Stark trap. After 20 hours the reaction was cooled to room temperature. The solution was poured into 1.5 L of ethyl ether, whereupon the p-toluenesulfonic acid salt of the benzyl ester of valine precipitated. To this thick suspension was added 1.3 L of water and solid sodium carbonate until the solution was alkaline. The aqueous phase was washed with ethyl ether, then the organic layers were combined and extracted with 1 L of 3M phosphoric acid. The organic solvent was discarded, and the aqueous layer was made basic by addition of 4.0M sodium hydroxide. Methylene chloride was added and the mixture was cooled to about 0° C., then 133.11 g (850 mmol) of phenylchloroformate was added over a two minute period. The reaction solution was stirred for one hour, the organic layer was separated and 5 mL of N,N-dimethylethylenediamine was added with mixing. The organic solution was washed once with 1 L of 1N HCl, dried over MgSO4, filtered and concentrated in vacuo, to afford 231.5 g of the title product as a clear syrup. NMR (CDCl3) δ:0.91 (d,3H), 1.02 (d,3H), 2.25 (m, 1H), 4.41 (q, 1H), 5.22 (dd,2H), 5.52 (d,1H), 7.12 (m,2H), 7.20 (m,2H), 7.39 (m, 6H).

Workup

  1. temperatureheated
  2. temperatureto reflux in an apparatus
  3. customfitted with a Dean-Stark trap
  4. customprecipitated
  5. additionTo this thick suspension was added 1.3 L of water and solid sodium carbonate until the solution
  6. washThe aqueous phase was washed with ethyl ether
  7. extractionextracted with 1 L of 3M phosphoric acid
  8. additionthe aqueous layer was made basic by addition of 4.0M sodium hydroxide
  9. additionMethylene chloride was added
  10. temperaturethe mixture was cooled to about 0° C.
  11. customthe organic layer was separated
  12. addition5 mL of N,N-dimethylethylenediamine was added
  13. additionwith mixing
  14. washThe organic solution was washed once with 1 L of 1N HCl
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1381532d08ca4f85931e20a9ee382dea
Source dataset
uspto-grants-1994_11
Patent number
US05362912

Reaction notes

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