Triethylamine → Boc-N-Methyl-L-Leucyl-L-Valyl-N-Methyl-L-Alanyl-L-Alanine Benzyl Ester

HRID 2072758Notes

Reaction equation

HRID 2072758 reaction equation
[C:1]([N:8]([CH3:17])[C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.[CH2:25]([O:32][C:33](=[O:50])[C@H:34]([CH3:49])[NH:35][C:36](=[O:48])[C@H:37]([CH3:47])[N:38]([C:40](=[O:46])[C@H:41]([CH:43]([CH3:45])[CH3:44])[NH2:42])[CH3:39])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>ClCCl>[CH2:25]([O:32][C:33](=[O:50])[C@H:34]([CH3:49])[NH:35][C:36](=[O:48])[C@H:37]([CH3:47])[N:38]([C:40](=[O:46])[C@H:41]([CH:43]([CH3:45])[CH3:44])[NH:42][C:14](=[O:16])[C@H:9]([CH2:10][CH:11]([CH3:12])[CH3:13])[N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH3:17])[CH3:39])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 7010555(2S)-2-{[(tert-butoxy)carbonyl](methyl)amino}-4-methylpentanoic acidHCID 14673108L-Valyl-N-Methyl-L-Alanyl-L-Alanine Benzyl Ester

Product 1

HCID 14673110Boc-N-Methyl-L-Leucyl-L-Valyl-N-Methyl-L-Alanyl-L-Alanine Benzyl Ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3.17 g (0.0537 mole) of Boc-N-methyl-L-leucine in 370 ml of dry dichloromethane was stirred and cooled at 0° C. as one-half of 13.15 g. (0.130 mole) of dry triethylamine was added, followed by 15.05 g (0.0591 mole) of BOP-CCl. This was stirred at 0° C. for 3 hours. The remainder of the triethylamine was added, followed by a solution of 13 g (0.0358 mole) of L-valyl-N-methyl-L-alanyl-L-alanine benzyl ester in 50 ml of dry dichloromethane. The reaction was stirred at ice temperature for 22 hours, then washed with 125 ml of a 10% solution of potassium bisulfate. The organic layer was further washed with 2×100 ml of saturated sodium bicarbonate solution, dried over magnesium sulfate, concentrated to a small volume, and chromatographed on silica gel eluting with 1:1 ether/hexane gradually increasing the ether to 2:1. The product weighed 15.8 g (75% of theory), and the FAB m.s. showed a molecular ion peak at 591.

Workup

  1. stirringThe reaction was stirred at ice temperature for 22 hours
  2. washwashed with 125 ml of a 10% solution of potassium bisulfate
  3. washThe organic layer was further washed with 2×100 ml of saturated sodium bicarbonate solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated to a small volume
  6. customchromatographed on silica gel eluting with 1:1 ether/hexane
  7. temperaturegradually increasing the ether to 2:1

Sources & evidence

ORD record
ord-8fcd1eb197fb4a91a4ff9a09ed4e6c6d
Source dataset
uspto-grants-1990_04
Patent number
US04914188

Reaction notes

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