Dicyclohexylcarbodiimide → HCID 13727808, compound

HRID 1583687Notes

Reaction equation

HRID 1583687 reaction equation
[C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]([C:17]([OH:19])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C1C=CC=CN=1)C.[CH3:29][Si:30]([CH3:35])([CH3:34])[CH2:31][CH2:32]O.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]([C:17]([O:19][CH2:32][CH2:31][Si:30]([CH3:35])([CH3:34])[CH3:29])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 180132-(Trimethylsilyl)ethanolHCID 218852-DimethylaminopyridineHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-

Product 1

HCID 13727808HCID 13727808, compoundYield 70.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 20.1 g (75.7 mmol) of [(phenylmethoxy)carbonyl]-L-leucine, 0.925 g (7.57 mmol) of dimethylaminopyridine and 8.95 g (75.7 mmol) of 2-trimethylsilylethanol in 200 ml of dichloromethane was cooled in an ice bath under nitrogen and treated with a solution of 15.6 g (75.7 mmol) of dicyclohexylcarbodiimide in 50 ml of dichloromethane. The ice bath was removed after 30 minutes and the reaction allowed to come to room temperature overnight. The reaction mixture was filtered, concentrated in vacuo and partitioned between 800 ml of ether and 200 ml of water. The organic layer was separated and further rinsed with saturated sodium bicarbonate, water, 10% potassium bisulfate, water and brine, then dried (magnesium sulfate) and concentrated in vacuo to 26.1 g of crude product. Flash filtration over silica gel (180 g in 20:1, hexanes:ethyl acetate) yielded 22.9 g of crude product which was chromatographed using a Waters Prep 500 LC, two columns eluted with 15:1, hexanes:ethyl acetate (250 ml/minute, 200 ml fractions). Combining the pure fractions yielded 19.6 g of the title compound as an oil: [α]D =7.3° (c=1, chloroform).

Workup

  1. temperaturewas cooled in an ice bath under nitrogen
  2. customThe ice bath was removed after 30 minutes
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated in vacuo
  5. custompartitioned between 800 ml of ether and 200 ml of water
  6. customThe organic layer was separated
  7. washfurther rinsed with saturated sodium bicarbonate, water, 10% potassium bisulfate, water and brine
  8. dry with materialdried (magnesium sulfate)
  9. concentrationconcentrated in vacuo to 26.1 g of crude product
  10. filtrationFlash filtration over silica gel (180 g in 20:1, hexanes:ethyl acetate)
  11. customyielded 22.9 g of crude product which
  12. customwas chromatographed
  13. washeluted with 15:1, hexanes

Sources & evidence

ORD record
ord-04389346834f4a2592bfc02779682923
Source dataset
uspto-grants-1985_11
Patent number
US04552866

Reaction notes

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