Citric Acid → Phenylmethyl N-[(5S)-5-[[(1,1-dimethylethoxy)carbonyl]amino]-6-oxohexyl]carbamate

HRID 2302206Notes

Reaction equation

HRID 2302206 reaction equation
[NH:1]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:2]([C:18](OC)=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].[H-].C([Al+]CC(C)C)C(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.CCCCCC>[NH:1]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:2]([CH:18]=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:9]

Participants

6

Reactant 3

HCID 311Citric AcidHCID 11132998Boc-L-Lys(Z)-OMeHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 11100590Phenylmethyl N-[(5S)-5-[[(1,1-dimethylethoxy)carbonyl]amino]-6-oxohexyl]carbamateYield 102.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

To a solution of 0.975 g of Boc-Lys(Cbz)-OMe in 25 ml of dichloromethane at −78° C. under a nitrogen atmosphere was added 6 ml of a 1M diisobutylaluminiumhydride solution in hexane. After 15 min the reaction was completed, the reaction mixture poured into 150 ml of 2% citric acid solution and filtered. The organic layer was separated, washed with water and brine, dried (magnesium sulfate) and concentrated. The residue was coevaporated with toluene to give 0.92 g of Boc-Lys(Cbz)-H. This aldehyde (0.89 g) was dissolved in 1.4 ml of toluene and 0.90 g of 2-(trimethylsilyl)oxazole (prepared according to: Edwards, P. D., Wolanin, D. J., Andisik D. W., and Davis W., J. Med. Chem. 38, 76 (1995)) was added and heated at 80° C. After 60 h the reaction mixture was concentrated, the residue dissolved in 5 ml of tetrahydrofuran, treated with 3 ml of a 3M tetrabutylammonium fluoride in tetrahydrofuran solution and stirred at room temperature for 2 h. The mixture was concentrated dissolved in ethyl acetate, washed with 3% aqueous sodium hydrogencarbonate solution and brine, dried (magnesium sulfate) and evaporated. Purification by column chromatography on silica gel eluting with a gradient of ethyl acetate/dichloromethane=2/1 (v/v) to ethyl acetate afforded an oil that was rechromatographed on silica gel eluting with a gradient of ethyl acetate/heptane=1/1 (v/v) to ethyl acetate/heptane=1/3 (v/v) to give 0.22 g of the title compound.

Workup

  1. filtrationfiltered
  2. customThe organic layer was separated
  3. washwashed with water and brine
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-2c219d830d3245a49acfaf8fc70ea650
Source dataset
uspto-grants-2002_08
Patent number
US06432921B1

Reaction notes

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