Dicyclohexylamine → BOC-Nva-Leu-OMe

HRID 851716

Reaction equation

HRID 851716 reaction equation
[NH:1]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:2]([C:6]([OH:8])=O)[CH2:3][CH2:4][CH3:5].C1CCC(NC2CCCCC2)CC1.[NH2:29][C@H:30]([C:35]([O:37][CH3:38])=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33].Cl.C(N(CC)CC)C.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)(Cl)Cl>[NH:1]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:2]([C:6]([NH:29][C@H:30]([C:35]([O:37][CH3:38])=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33])=[O:8])[CH2:3][CH2:4][CH3:5]

Participants

7

Reactant 5

HCID 7582DicyclohexylamineHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 2723695Leucine methyl ester hydrochlorideHCID 2733748(2S)-2-(((tert-butoxy)carbonyl)amino)pentanoic acid

Product 1

HCID 57262488BOC-Nva-Leu-OMeYield 75%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

BOC-Nva-OH, liberated from 8.0 g (20 mmoles) of the DCHA salt as described in Step 1 of Example 4, and 3.82 g (21 mmoles) of H-Leu-OMe.HCl are dissolved in 60 ml of chloroform, and 2.94 ml (21 mmoles) of triethylamine are added. The solution is cooled with ice, and a solution of 4.33 g (21 mmoles) of DCC in 40 ml of chloroform is added with stirring. The reaction mixture is allowed to stand at 5° C. overnight, the separated DCU is removed by filtration, the filtrate is washed thrice with 30 ml of n hydrochloric acid, each, thrice with 30 ml of n sodium hydrocarbonate solution, each, and finally with 30 ml of water, dried over anhydrous sodium sulfate, and then evaporated. The crystalline residue is triturated with n-hexane, filtered off, and the resulting 6.65 g of crude product is recrystallized from a mixture of 5 ml of ethyl acetate and 20 ml of petroleum ether. 5.20 g (75%) of BOC-Nva-Leu-OMe are obtained; m.p.: 100°-101° C., Rf2 =0.84, [α]D25 =-47.5° (c=1%, in methanol).

Workup

  1. temperatureThe solution is cooled with ice
  2. customthe separated DCU is removed by filtration
  3. washthe filtrate is washed thrice with 30 ml of n hydrochloric acid
  4. dry with materialeach, thrice with 30 ml of n sodium hydrocarbonate solution, each, and finally with 30 ml of water, dried over anhydrous sodium sulfate
  5. customevaporated
  6. customThe crystalline residue is triturated with n-hexane
  7. filtrationfiltered off
  8. customthe resulting 6.65 g of crude product is recrystallized from a mixture of 5 ml of ethyl acetate and 20 ml of petroleum ether

Sources & evidence

ORD record
ord-2948153d675a4c4a804ecc6dba33007e
Source dataset
uspto-grants-1983_05
Patent number
US04386073

Linked notes

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