Dicyclohexylcarbodiimide → N-(tert-Butoxycarbonyl)-L-leucine methyl ester

HRID 476798Notes

Reaction equation

HRID 476798 reaction equation
[CH:1](N(C(C)C)CC)(C)C.[CH3:10][C:11]([CH3:28])([O:13][C:14]([NH:16][C@H:17]([C:25]([OH:27])=[O:26])[CH2:18][C:19]1[CH:24]=CC=C[CH:20]=1)=[O:15])[CH3:12].N[C@H](C(OC)=O)CC(C)C.O.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[CH3:10][C:11]([CH3:28])([O:13][C:14]([NH:16][C@H:17]([C:25]([O:27][CH3:1])=[O:26])[CH2:18][CH:19]([CH3:24])[CH3:20])=[O:15])[CH3:12]

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 65105(+)-L-Leucine methyl esterHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 10879384N-(tert-Butoxycarbonyl)-L-leucine methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of diisopropylethylamine (8.7 ml., 50 mmole) in tetrahydrofuran (50 ml.) is added dropwise to a mixture of N-[(1,1-dimethylethoxy) carbonyl]-L-phenylalanine (13.265 g., 50 mmole), L-leucine, methyl ester (9.085 g., 50 mmole) and 1-hydroxybenzotriazole hydrate (7.65 g., 50 mmole) in tetrahydrofuran (100 ml.) at 0°. This is followed by the addition of dicylcohexylcarbodiimide (10.315 g., 50 mmole). The reaction is stirred at 0°for 2 hours and left stirring overnight at room temperature. The nexy day, the precipitated dicyclohexyl urea is filtered off, the solvents are stirred down and the residue is diluted with ethyl acetate (200 ml.). The organic solution is washed sequentially with saturated aqueous sodium bicarbonate solution (2×100 ml.) and saturated aqueous sodium chloride (2×100 ml.), dried over sodium sulfate, filtered, and concentrated to give crude product. Crystallization from ethyl ether gives 7.05 g. of pure product. Concentration of the mother liquor solutions gives 4.57 g. of crystalline product. An additional 1.35 g. of product is obtained by chromatographic purification of the crude product obtained from the left-over mother liquors (40 g. silica gel, eluting with 4:1 hexane:ethyl acetate). Thus, a total of 12.96 g. of N-[N-[(1,1 -dimethylethoxy)carbonyl]-L-leucine, methyl ester is obtained;

Workup

  1. waitleft
  2. stirringstirring overnight at room temperature
  3. filtrationThe nexy day, the precipitated dicyclohexyl urea is filtered off
  4. stirringthe solvents are stirred down
  5. additionthe residue is diluted with ethyl acetate (200 ml.)
  6. washThe organic solution is washed sequentially with saturated aqueous sodium bicarbonate solution (2×100 ml.) and saturated aqueous sodium chloride (2×100 ml.)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give crude product
  11. customCrystallization from ethyl ether
  12. customgives 7.05 g
  13. customConcentration of the mother liquor solutions gives 4.57 g
  14. customof product is obtained by chromatographic purification of the crude product
  15. customobtained from the
  16. washleft-over mother liquors (40 g. silica gel, eluting with 4:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-7bfc219691bb4434a16bcfc3d99525e4
Source dataset
uspto-grants-1989_12
Patent number
US04885292

Reaction notes

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