4-Methylmorpholine → Boc-leu-leu-ome

HRID 849685Notes

Reaction equation

CN1CCOCC1.O.[C:9]([NH:16][C@H:17]([C:22]([OH:24])=O)[CH2:18][CH:19]([CH3:21])[CH3:20])([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C1C=CC2N(O)N=NC=2C=1.[NH2:35][C@H:36]([C:41]([O:43][CH3:44])=[O:42])[CH2:37][CH:38]([CH3:40])[CH3:39].Cl.C1CCC(N=C=NC2CCCCC2)CC1>C(OCC)(=O)C>[NH:16]([C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[C@H:17]([C:22]([NH:35][C@H:36]([C:41]([O:43][CH3:44])=[O:42])[CH2:37][CH:38]([CH3:40])[CH3:39])=[O:24])[CH2:18][CH:19]([CH3:20])[CH3:21]

Participants

Conditions

Temperature: 20 °C

Procedure

4-Methylmorpholine (12.62 g, 124.8 mmol), Boc-Leucine monohydrate (29.92, 120.0 mmol) and HOBt (1.62 g, 12.0 mmol) were added to a solution of H-Leu-OMe·HCl (21.80 g, 120.0 mmol) in ethyl acetate (205 g). A solution of DCC (29.71 g, 144.0 mmol) in ethyl acetate (25.0 g) was added at 0 to 5° C. over 30 min and the resulting mixture was stirred over 2 h at a maximum temperature of 20° C. The resulting urea was removed by filtration and washed with ethyl acetate and the combined organic filtrate was extracted with successive portions of 5% aq. K2CO3 and 5% aq. KHSO4. The organic layer was dried (MgSO4), concentrated in vacuo, and the residual solid was recrystallized from petroleum ether (bp 100-125° C.) to give Boc-Leu-Leu-OMe (38.6 g, 89.8%).

Workup

customThe resulting urea was removed by filtration
washwashed with ethyl acetate
extractionthe combined organic filtrate was extracted with successive portions of 5% aq. K2CO3 and 5% aq. KHSO4
dry with materialThe organic layer was dried (MgSO4)
concentrationconcentrated in vacuo
customthe residual solid was recrystallized from petroleum ether (bp 100-125° C.)

Sources & evidence

ORD record: ord-60b4c7e3dcd64bfc8bc363a2c64fcc30
Source dataset: uspto-grants-2000_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06013764

Reaction notes

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