Diethyl squarate → [3-[[(1,1-Dimethylethyloxycarbonyl)methyl]-(2-ethoxy-3,4-dioxo-1-cyclobuten-1-yl)amino]propyl]carbamic acid phenylmethyl ester
Reaction equation
[C:1]1([CH2:7][O:8][C:9](=[O:23])[NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:24]([O:26][C:27]1[C:28](=O)[C:29](=[O:34])[C:30]=1[O:31]CC)[CH3:25]>>[C:1]1([CH2:7][O:8][C:9](=[O:23])[NH:10][CH2:11][CH2:12][CH2:13][N:14]([CH2:15][C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[C:28]2[C:29](=[O:34])[C:30](=[O:31])[C:27]=2[O:26][CH2:24][CH3:25])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1Participants
Procedure
An ethanolic solution (60 mL) of [3-[[(1,1-dimethylethyloxycarbonyl)-methyl]amino]propyl]carbamic acid phenylmethyl ester (4.49 g, 13.9 mmol) under nitrogen was added to 3,4-diethoxy-3-cyclobutene-1,2-dione (2.0 mL, 13 mmol) in the same solvent (60 mL) over 1 hour. After 3.5 more hours, the reaction mixture was preadsorbed onto silica gel and purified by flash chromatography (7.5 cm diameter, gradient elution with 30 to 60% ethyl acetate in petroleum ether) to afford [3-[[(1,1-dimethylethyloxycarbonyl)methyl]-(2-ethoxy-3,4-dioxo-1-cyclobuten-1-yl)amino]-propyl]carbamic acid phenylmethyl ester as a viscous colorless oil (5.26 g, 91%); MS (+CI): 447 (MH+, 100), 391 (38); 1H NMR (CDCl3, 400 MHz): δ 7.35 (m, 5H), 5.55, 4.97 (br m, NH), 5.10 (s, 2H), 4.75, 4.73 (q, J=7 Hz, 2H), 4.29, 3.99 (s, 2H), 3.74, 3.49 (t, J=6.5 Hz, 2H), 3.29-3.22 (m, 2H), 1.84-1.75 (m, 2H), 1.48, 1.47 (s, 9H), 1.45-1.40 (m, 3H).
Workup
- custompurified by flash chromatography (7.5 cm diameter, gradient elution with 30 to 60% ethyl acetate in petroleum ether)
Sources & evidence
- ORD record
- ord-1f636bd29a1b42f9ba40f6213f0600c5
- Source dataset
- uspto-grants-1992_12
- Patent number
- US05168103
Reaction notes
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