Morpholine → Methyl 3-(morpholinosulfonyl)-5-(trifluoromethyl)benzoate
Reaction equation
Cl[S:2]([C:5]1[CH:6]=[C:7]([CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1)[C:8]([O:10][CH3:11])=[O:9])(=[O:4])=[O:3].C(N(C(C)C)C(C)C)C.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:11][O:10][C:8](=[O:9])[C:7]1[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=[C:5]([S:2]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)(=[O:4])=[O:3])[CH:6]=1Participants
Procedure
To an ice-cold solution of methyl 3-(chlorosulfonyl)-5-(trifluoromethyl)benzoate (1.0 g, 3.3 mmol, Buttpark Ltd.) in dichloromethane (10 mL) was added N-ethyldiisopropylamine (854 mg, 1.15 mL, 6.61 mmol) and morpholine (317 mg, 317 μL, 3.63 mmol). The reaction mixture was stirred at room temperature for 2 hours, poured on 10% aqueous sodium bicarbonate solution (100 mL) and dichloromethane (100 mL) and the layers were separated. The aqueous layer was extracted a second time with dichloromethane (100 mL). The organic layers were washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography on a 20 g column using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 35:65). Off-white solid (1.04 g, 89%). MS (EI): m/z=353.087 ([M]).
Workup
- customthe layers were separated
- extractionThe aqueous layer was extracted a second time with dichloromethane (100 mL)
- washThe organic layers were washed with brine (100 mL)
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated under vacuum
- customThe compound was purified by silica gel chromatography on a 20 g column
- washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 35:65)
Sources & evidence
- ORD record
- ord-9401dd491c1543069b9bd98d2360d322
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08748434B2
Reaction notes
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