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

HRID 2254529Notes

Reaction equation

HRID 2254529 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.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[CH2:40]([O:47][C:48](=[O:65])[C@H:49]([CH3:64])[NH:50][C:51](=[O:63])[C@H:52]([CH3:62])[N:53]([C:55](=[O:61])[C@H:56]([CH:58]([CH3:60])[CH3:59])[NH2:57])[CH3:54])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>ClCCl>[CH2:40]([O:47][C:48](=[O:65])[C@H:49]([CH3:64])[NH:50][C:51](=[O:63])[C@H:52]([CH3:62])[N:53]([C:55](=[O:61])[C@H:56]([CH:58]([CH3:60])[CH3:59])[NH:57][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])[CH3:54])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 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 13.17 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-Cl. 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-131d96b861e04059833588912923c89c
Source dataset
uspto-grants-1993_08
Patent number
US05236899

Reaction notes

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