4-Methylmorpholine → HCID 12020545, compound

HRID 1513526Notes

Reaction equation

HRID 1513526 reaction equation
ClC(OCC(C)C)=O.[NH:9]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@H:10]([C:26]([OH:28])=O)[CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].CN1CCOCC1.[NH2:43][C@H:44]([C:49]([NH:51][C@H:52]([C:57]([O:59][CH3:60])=[O:58])[CH2:53][CH:54]([CH3:56])[CH3:55])=[O:50])[CH2:45][CH:46]([CH3:48])[CH3:47].Cl>C(OCC)(=O)C>[NH:9]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@H:10]([C:26]([NH:43][C@H:44]([C:49]([NH:51][C@H:52]([C:57]([O:59][CH3:60])=[O:58])[CH2:53][CH:54]([CH3:55])[CH3:56])=[O:50])[CH2:45][CH:46]([CH3:47])[CH3:48])=[O:28])[CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]([O:18][CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:17]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 2724765Boc-Lys(Z)-OHHCID 15598024L-Leucine, L-leucyl-, methyl ester, hydrochloride (1:1)

Product 1

HCID 12020545HCID 12020545, compoundYield 90.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent7×

Procedure

Isobutyl chloroformate (13.66 g, 100 mmol) was added dropwise over 15 min at −15 to −10° C. to a solution of Boc-Lys(Z)—OH (38.04 g, 100 mmol) in ethyl acetate (200 g). Another portion of ethyl acetate was added (10 g) and the mixture was stirred for 15 min. 4-Methylmorpholine (10.12 g, 100 mmol) was added dropwise over 15 min at −15 to −10° C., followed by an additional portion of ethyl acetate (10.0 g) and the resulting mixture was stirred for 2 h. In a separate reaction vessel 4-methylmorpholine (10.12 g, 100 mmol) was added dropwise over 15 min, to a solution of H-Leu-Leu-OMe.HCl (29.48 g, 100 mmol) in ethyl acetate (200.0 g) at −23 to −10° C. An additional portion of ethyl acetate (10.0 g) was added followed by the addition of the formed anhydride over 30 to 45 min at a temperature of −8 to −10° C. Another portion of ethyl acetate (30.0 g) was added and the resulting mixture was stirred for 1.5 h. Ethyl acetate (50.00 g) was added, the solution was filtered and the resulting organic filtrate was concentrated in vacuo. The resulting solid was recrystallized from petroleum ether (bp 100 to 125) to give Boc-Lys(Z)-Leu-Leu-OMe (55.9 g, 90.2%).

Workup

  1. stirringthe resulting mixture was stirred for 2 h
  2. stirringthe resulting mixture was stirred for 1.5 h
  3. filtrationthe solution was filtered
  4. concentrationthe resulting organic filtrate was concentrated in vacuo
  5. customThe resulting solid was recrystallized from petroleum ether (bp 100 to 125)

Sources & evidence

ORD record
ord-7397d02040dd47f294d049d28bdeccfc
Source dataset
uspto-grants-2012_07
Patent number
US08217142B2

Reaction notes

Loading…