4-Methylmorpholine → n-Cyclobutyl-5-(2,6-dichloro-4-methoxymethyl-phenoxy)-2-methoxy-benzamide
Reaction equation
[Cl:1][C:2]1[CH:19]=[C:18]([CH2:20][O:21][CH3:22])[CH:17]=[C:16]([Cl:23])[C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([O:14][CH3:15])=[C:9]([CH:13]=1)[C:10]([OH:12])=O.C(OC(Cl)=O)C(C)C.CN1CCOCC1.[CH:39]1([NH2:43])[CH2:42][CH2:41][CH2:40]1>O1CCCC1.Cl>[CH:39]1([NH:43][C:10](=[O:12])[C:9]2[CH:13]=[C:5]([O:4][C:3]3[C:2]([Cl:1])=[CH:19][C:18]([CH2:20][O:21][CH3:22])=[CH:17][C:16]=3[Cl:23])[CH:6]=[CH:7][C:8]=2[O:14][CH3:15])[CH2:42][CH2:41][CH2:40]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
To a solution of the title compound of Step D (238 mg, 0.67 mmol) in tetrahydrofuran (7 ml) at 0° C. under nitrogen was added isobutylchloroformate (0.13 mL, 1 mmol) and N-methylmorpholine (0.15 ml, 1.3 mmol). After stirring for about 30 minutes at 0° C., cyclobutylamine (0.11 ml, 1.3 mmol) was added. The reaction mixture was warmed to room temperature and stirred for about 19 hours. The reaction solution was diluted with 1N HCl (30 ml) and extracted with ethyl acetate (3×15 ml). The combined organic extracts were washed with 1N HCl (2×50 ml), brine (50 ml), dried, filtered, and concentrated. The crude product was purified by preparative TLC (50% ethyl acetate in hexanes) to afford the title compound (170 mg) as a viscous oil. MS (APCl+) Calc: 409.1, found: 409.7 (M+1)
Workup
- temperatureThe reaction mixture was warmed to room temperature
- stirringstirred for about 19 hours
- extractionextracted with ethyl acetate (3×15 ml)
- washThe combined organic extracts were washed with 1N HCl (2×50 ml), brine (50 ml)
- customdried
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified by preparative TLC (50% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-72b6caa6f0944536bbd3245586624df7
- Source dataset
- uspto-grants-2003_09
- Patent number
- US06620830B2
Reaction notes
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