Hydrochloric Acid → Methyl Acetyl-L-leucyl-L-leucinate

HRID 1857671Notes

Reaction equation

HRID 1857671 reaction equation
[C:1]([NH:4][C@H:5]([C:10](O)=[O:11])[CH2:6][CH:7]([CH3:9])[CH3:8])(=[O:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[NH:28](Cl)[C@H:29]([C:34]([O:36][CH3:37])=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32].Cl>C1COCC1>[NH:4]([C:1]([CH3:2])=[O:3])[C@H:5]([C:10]([NH:28][C@H:29]([C:34]([O:36][CH3:37])=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32])=[O:11])[CH2:6][CH:7]([CH3:8])[CH3:9]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 70912N-Acetyl-L-leucineHCID 88276507HCl-LeuOMe

Product 1

HCID 14237508Methyl Acetyl-L-leucyl-L-leucinate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acetyl-Leucine (5.0 g) was dissolved in 150 mL of distilled THF under argon and the resulting solution was cooled to -15°. Next one equivalent of N-methyl morpholine followed by one equivalent of isobutyl chloroformate was added and the reaction was allowed to activate 20 minutes and then another equivalent of N-methyl morpholine followed by HCl-LeuOMe (5.25 g). The reaction is allowed to slowly come to room temperature and stir overnight. The reaction was then poured into 150 mL of 1N HCl and extracted with ethyl acetate (2×150 mL). The combined organic fractions were washed with 1N HCl (15 mL), brine (50 mL), and dried over MgSO4, filtered and the solvent was removed under reduced pressure and then high vacuum. TLC (silica gel, CHCl3 /isopropanol:95:5) showed the product Ac-Leu-Leu-OCH3 to be a single spot Rf 0.36. NMR (100 MHz) δ 0.95 (d, 12H), 1.5 (bs, 6H), 2.0 (s, 3H), 3.7 (s, 3H), 4.5 (q, 2H), 6.6 (d, 1H), 6.8 (d, 1H).

Workup

  1. temperaturethe resulting solution was cooled to -15°
  2. additionwas added
  3. customto slowly come to room temperature
  4. extractionextracted with ethyl acetate (2×150 mL)
  5. washThe combined organic fractions were washed with 1N HCl (15 mL), brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-d6078b804b4747428c7dfa02f1b57602
Source dataset
uspto-grants-2000_11
Patent number
US06147188

Reaction notes

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