Cyclobutanol → (S)-cyclobutyl 4-acetyl-7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate
Reaction equation
[CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.ClC(Cl)(O[C:10](=[O:16])OC(Cl)(Cl)Cl)Cl.C(N(CC)C(C)C)(C)C.[Br:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][CH:37]=1)[N:34]([C:38](=[O:40])[CH3:39])[C@@H:33]([CH3:41])[CH2:32][NH:31]2>ClCCCl>[C:38]([N:34]1[C:35]2[C:30](=[CH:29][C:28]([Br:27])=[CH:37][CH:36]=2)[N:31]([C:10]([O:5][CH:1]2[CH2:4][CH2:3][CH2:2]2)=[O:16])[CH2:32][C@@H:33]1[CH3:41])(=[O:40])[CH3:39]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 50 °C
Procedure
A solution of cyclobutanol (28.8 g, 399 mmol), 1,2-dichloroethane (450 mL), triphosgene (22.1 g, 74.41 mmol) and N,N-diisopropylethyl amine (58.0 mL, 333 mmol) was stirred at 50° C. for 2 hr. A solution of (S)-1-(6-bromo-2-methyl-3,4-dihydroquinoxaline-1(2H)-yl)ethan-1-one (10.0 g, 37.2 mmol) and N,N-diisopropylethyl amine (58.0 mL, 333 mmol) in 1,2-dichloroethane (180 mL) was added dropwise. The resulting solution was stirred for 5 h at 50° C. After cooling to room temperature, the reaction mixture was concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 25% ethyl acetate-petroleum ether) to afford cyclobutyl (S)-4-acetyl-7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (20 g, 73%) as yellow oil. MS (ESI, pos. ion) m/z 367, 369 [M+1]+.
Workup
- temperatureAfter cooling to room temperature
- concentrationthe reaction mixture was concentrated under vacuum
- customThe residue was purified via column chromatography on silica gel (eluting with 25% ethyl acetate-petroleum ether)
Sources & evidence
- ORD record
- ord-f82105ce95b84b70877ea3cde174b0af
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09422281B2
Reaction notes
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