Triethylamine → 4-fluoro-3-hydroxy-N-methoxy-N-methylbenzamide
Reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl.[CH3:31][NH:32][O:33][CH3:34]>C(Cl)Cl>[F:11][C:10]1[CH:9]=[CH:8][C:4]([C:5]([N:32]([O:33][CH3:34])[CH3:31])=[O:7])=[CH:3][C:2]=1[OH:1]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To a 5 L four necked round bottom flask was added 3-hydroxy-4-fluorobenzoic acid (100 g, 0.64 mol) and CH2Cl2 (2.3 L). Triethylamine (107 mL, 0.768 mol) was then added to the suspension. The solution was cooled to ±78° C., and EDCI (184.2 g, 0.961 mol) was added portion wise followed by the addition of N,O-dimethylhydroxyamine hydrochloride (93.6 g, 0.96 mol). The reaction mixture was stirred at −78° C. for 1 h and then allowed to warm to 0° C. over a period of 2 h. The reaction mixture was transferred to a separatory funnel and washed water (2×1.2 L). The organic portion was dried over Na2SO4, filtered and concentrated in vacuo to give 4-fluoro-3-hydroxy-N-methoxy-N-methylbenzamide as a white solid (94.4 g, 74%).
Workup
- temperatureThe solution was cooled
- customto ±78° C.
- temperatureto warm to 0° C. over a period of 2 h
- customThe reaction mixture was transferred to a separatory funnel
- washwashed water (2×1.2 L)
- dry with materialThe organic portion was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-4194de2991e94c6b8ca22e0a4614e989
- Source dataset
- uspto-grants-2010_09
- Patent number
- US07790770B2
Reaction notes
Loading…