Acetonitrile → HCID 57276549, compound

HRID 1248634Notes

Reaction equation

[CH3:1][C:2]([O:5][C:6](=[O:13])[C@H:7]([CH2:9][CH:10]([CH3:12])[CH3:11])[NH2:8])([CH3:4])[CH3:3].[C:14](#[N:16])[CH3:15]>>[O:5]=[C:2]([NH:8][C@H:7]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:13])[CH2:9][CH:10]([CH3:11])[CH3:12])[CH2:1][CH2:15][CH:14]1[CH2:9][CH2:7][C:6](=[O:13])[NH:16]1

Participants

Reactant 2

HCID 6342Acetonitrile

HCID 7022311tert-butyl (2S)-2-amino-4-methylpentanoate

Product 1

HCID 57276549HCID 57276549, compound

Conditions

Temperature: 80 °C

Procedure

A solution of 7.0 g (0.05 mol) of dihydro-1H-3,5(2H,6H)dioxopyrrolizidine in 150 ml of acetonitrile is treated with 14.05 g (0.075 mol) L-Leucine 1,1-dimethylethyl ester. The mixture is refluxed 24 hours. The solution is concentrated under reduced pressure and the resulting oil is chromatographed over silica gel using elution with 2.5% methanol in dichloromethane. After concentration at reduced pressure, the oil is rechromatographed over silica gel using 19:1 dichloromethane:methanol. The eluate is concentrated at reduced pressure and heated at 80° C. to yield N-[1-oxo-3-(5-oxo-2-pyrrolidinyl)-propyl]-L-leucine, 1,1-dimethylethyl ester as an analytically pure oil with the following characteristic proton NMR spectrum: 1H-NMR(CDCL3) 0.92(d, 6H), 1.42 (s, 9H), 1.4-1.9 (m, 5H), 2.2-2.4 (m, 7H), 3.5-3.8 (m, 1H), 4.2-4.5 (m, 1H), 6.25-6.5 (m, 1H).

Workup

temperatureThe mixture is refluxed 24 hours
concentrationThe solution is concentrated under reduced pressure
customthe resulting oil is chromatographed over silica gel using elution with 2.5% methanol in dichloromethane
concentrationAfter concentration at reduced pressure
customthe oil is rechromatographed over silica gel using 19:1 dichloromethane
concentrationThe eluate is concentrated at reduced pressure

Sources & evidence

ORD record: ord-f7eac78f6f84472ea62c950ccade7741
Source dataset: uspto-grants-1985_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04525476

Reaction notes

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