Acetic Acid → benzyl (S)-1-((1S,2R,4R)-2-ethyl-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

HRID 1374312Notes

Reaction equation

[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[CH2:12][CH2:11][C@H:10]([NH:13][C:14](=[O:23])[O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:9]2=[O:24])[C@H:4]([CH2:25][CH3:26])[CH2:3]1.[C:27](O)(=O)C.[CH3:31][C:32]([CH3:34])=O>ClCCCl>[CH2:25]([C@@H:4]1[CH2:3][C@H:2]([N:1]([CH:32]([CH3:34])[CH3:31])[CH3:27])[CH2:7][CH2:6][C@@H:5]1[N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14](=[O:23])[O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:9]1=[O:24])[CH3:26]

Participants

Conditions

Temperature: 50 °C

Procedure

The benzyl (S)-1-((1S,2R,4R)-4-amino-2-ethylcyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (assumed 2.2 mmol) was dissolved in 1,2-dichloroethane (27 mL) and the resulting solution was charged successively with acetic acid (0.27 mL), acetone, and NaHB(OAc)3 (1.15 g) before being heated to 50° C. for 18 h. The reaction was concentrated in vacuo and the residue was dissolved in acetonitrile. The resulting solution was charged successively with formaldehyde and sodium cyanoborohydride. The reaction was concentrated in vacuo and purified via flash chromatography to afford benzyl (S)-1-((1S,2R,4R)-2-ethyl-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (607 mg). MS found: (M+H)+=416.3.

Workup

concentrationThe reaction was concentrated in vacuo
dissolutionthe residue was dissolved in acetonitrile
additionThe resulting solution was charged successively with formaldehyde and sodium cyanoborohydride
concentrationThe reaction was concentrated in vacuo
custompurified via flash chromatography

Sources & evidence

ORD record: ord-5c483cba4cb9463dad9f459d34ee7240
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07163937B2

Reaction notes

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