4-Methylmorpholine → Z-Asp(OtBu)-Leu-OBzl

HRID 1700077Notes

Reaction equation

HRID 1700077 reaction equation
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([OH:13])=O)[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:39][C@H:40]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[CH2:41][CH:42]([CH3:44])[CH3:43]>C1COCC1.C(N(CC)CC)C>[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([NH:39][C@H:40]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[CH2:41][CH:42]([CH3:44])[CH3:43])=[O:13])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:7])([CH3:8])[CH3:9]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 1110824-tert-Butyl hydrogen N-((phenylmethoxy)carbonyl)-L-aspartateHCID 6451313Benzyl L-leucinate

Product 1

HCID 131721133Z-Asp(OtBu)-Leu-OBzl

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Z-Asp(OtBu)-OH (10.23 g) in THF (50 mL) was added N-methylmorpholine (3.30 mL) and isobutyl chloroformate (3.90 mL) at −20° C. After 10 min, the reaction mixture was added to the solution of H-Leu-OBzl (11.81 g in 50 mL HCl3) at −20° C., followed by addition of triethylamine (4.18 mL). The resulting mixture was allowed to warm to room temp. After filtering off the salt, the filtrate was concentrated to an oil. The oil was dissolved in 100 mL of ethyl acetate; washed with 0.2 N HCl, 5% NaHCO3 and sat. NaCl; dried over Na2SO4. After filtration, the solvent was evaporated to give Z-Asp(OtBu)-Leu-OBzl as an oil of 14.81 g.

Workup

  1. filtrationAfter filtering off the salt
  2. concentrationthe filtrate was concentrated to an oil
  3. dissolutionThe oil was dissolved in 100 mL of ethyl acetate
  4. washwashed with 0.2 N HCl, 5% NaHCO3 and sat. NaCl
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration
  7. customthe solvent was evaporated

Sources & evidence

ORD record
ord-93d596ac90764912a5cd60996356945b
Source dataset
uspto-grants-2002_02
Patent number
US06350573B1

Reaction notes

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