Triethylamine → 4-(2-Fluorobenzoyl)-3-(hydroxymethyl)morpholine
Reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][O:7][CH2:6][CH2:5][NH:4]1.[F:9][C:10]1[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=1[C:12](Cl)=[O:13].C(N(CC)CC)C.[OH-].[Na+]>ClCCl>[F:9][C:10]1[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=1[C:12]([N:4]1[CH2:5][CH2:6][O:7][CH2:8][CH:3]1[CH2:2][OH:1])=[O:13]Participants
Procedure
To a solution of 3-(hydroxymethyl)morpholine (345 mg; 2.95 mmol) in dichloromethane (10 mL) was carefully added 2-fluorobenzoyl chloride (0.35 mL; 2.95 mmol) and triethylamine (0.62 mL; 4.42 mmol) and the reaction stirred for 0.5 h. The product was combined with 4 N NaOH (10 mL) to hydrolyse any ester and the organic layer extracted (dichloromethane, 3×). The combined organic layers were dried (Na2SO4) and the solvent evaporated to give an oil, which was purified by flash column chromatography on silica (gradient elution, dichloromethane-methanol 1:0 to 9:1) to give 4-(2-fluorobenzoyl)-3-(hydroxymethyl)morpholine (165 mg; 0.69 mmol), EIMS: m/z=240.2 (M+H)+. This product and caesium carbonate (0.544 g) were heated to 120° C. in dimethylformamide (10 ml) solution under nitrogen for 4 hours. The solvent was evaporated, and the residue taken up in water and extracted with dichloromethane (3×). The combined dichloromethane extracts were dried (Na2SO4) and the solvent evaporated to give a crude solid which was purified by flash column chromatography on silica, eluting with ether to give the title compound (77 mg). M.p. 105-107° C.; EIMS: m/z=220.2 (M+H)+.
Workup
- extractionthe organic layer extracted (dichloromethane, 3×)
- dry with materialThe combined organic layers were dried (Na2SO4)
- customthe solvent evaporated
- customto give an oil, which
- customwas purified by flash column chromatography on silica (gradient elution, dichloromethane-methanol 1:0 to 9:1)
Sources & evidence
- ORD record
- ord-9f6900f7a80e49c0abab2c878ff8e88b
- Source dataset
- uspto-grants-2009_03
- Patent number
- US07504390B2
Reaction notes
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