Dimethyl Sulfoxide → Benzyl 3-(3-chloropyrazin-2-yloxy)azetidine-1-carboxylate
Reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH:13]([OH:15])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:16][C:17]1[C:22](Cl)=[N:21][CH:20]=[CH:19][N:18]=1.CS(C)=O.CC(C)([O-])C.[Na+]>O>[Cl:16][C:17]1[C:22]([O:15][CH:13]2[CH2:14][N:11]([C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])[CH2:12]2)=[N:21][CH:20]=[CH:19][N:18]=1Participants
Procedure
To a solution of 3-hydroxy-azetidine-1-carboxylic acid benzyl ester (5.19 g, 27.4 mmol, purchased from Ace Synthesis), 2,3-dichloropyrazine (4.116 g, 27.6 mmol, Oakwood) and DMSO (40 mL) was added sodium tert-butoxide (2.64 g, 27.4 mmol) in three portions. The solution was allowed to stir at room temperature. After 2 hours, the reaction was poured into water (200 mL) and the aqueous solution was extracted with ether (3×50 mL). The combined ether layers were washed with water (50 mL), brine (50 mL), and then concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (80 g), eluting with 0% to 20% EtOAc in hexane, to provide benzyl 3-(3-chloropyrazin-2-yloxy)azetidine-1-carboxylate (5.4 g, 61.6% yield), as a yellow oil. MS (ESI) m/z 320.1 (MH+). IC50 (uM): 1.33.
Workup
- extractionthe aqueous solution was extracted with ether (3×50 mL)
- washThe combined ether layers were washed with water (50 mL), brine (50 mL)
- concentrationconcentrated in vacuo
- customchromatographed through a Redi-Sep® pre-packed silica gel column (80 g)
- washeluting with 0% to 20% EtOAc in hexane
Sources & evidence
- ORD record
- ord-e30a6f8f590346f081ff6b5f1f661a95
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376450B2
Reaction notes
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