Nordiazepam → Methyl 4-(cyclopropanesulfonamido)bicyclo[2.2.2]octane-1-carboxylate
Reaction equation
[NH2:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]([O:12][CH3:13])=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C1C=CC(C2C3C=C(Cl)C=CC=3NC(=O)CN=2)=CC=1.[CH:33]1([S:36](Cl)(=[O:38])=[O:37])[CH2:35][CH2:34]1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:33]1([S:36]([NH:1][C:2]23[CH2:3][CH2:4][C:5]([C:10]([O:12][CH3:13])=[O:11])([CH2:8][CH2:9]2)[CH2:6][CH2:7]3)(=[O:38])=[O:37])[CH2:35][CH2:34]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (500 mg, 2.73 mmol) (Yeh, V. S. C.; Kurukulasuriya, R.; Madar, D.; Patel, J. R.; Fung, S.; Monzon, K.; Chiou, W.; Wang, J.; Jacobson, P.; Sham, H. L.; Link, J. T. Bioorg. and Med. Chem. Let, 2006, vol. 16, #20 p. 5408-5413) in DCM (10 mL) at rt was added TEA (0.76 mL, 5.46 mmol) and DMAP (50 mg, 0.41 mmol). Cyclopropanesulfonyl chloride (764 mg, 5.46 mmol, Matrix) was added dropwise by syringe. The reaction mixture was stirred for about 15 h at rt. The mixture was washed with water (10 mL), and the aqueous layer was extracted with DCM (2×10 mL), the organic layers were combined and dried over anhydrous Na2SO4, filtered and concd in vacuo. The crude materials was purified by silica gel chromatography eluting with a gradient of 20-35% EtOAc in hexanes to afford methyl 4-(cyclopropanesulfonamido)bicyclo[2.2.2]octane-1-carboxylate (410 mg, 52% yield). LC/MS (Table 1, Method p) Rt=1.68 min; MS m/z: 288 (M+H)+.
Workup
- washThe mixture was washed with water (10 mL)
- extractionthe aqueous layer was extracted with DCM (2×10 mL)
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- customThe crude materials was purified by silica gel chromatography
- washeluting with a gradient of 20-35% EtOAc in hexanes
Sources & evidence
- ORD record
- ord-108472bee9c84adeb0eb5189b9eb138b
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08426411B2
Reaction notes
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