Hydrochloric Acid → Methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate
Reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([C:14]1[CH:15]=[C:16]([CH:21]=[C:22]([Br:25])[C:23]=1[OH:24])[C:17]([O:19][CH3:20])=[O:18])(=[O:13])[CH3:12].[N:26]1([C:32](Cl)=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.Cl>C1COCC1.O.C(Cl)Cl>[Br:25][C:22]1[CH:21]=[C:16]([CH:15]=[C:14]([C:11](=[O:13])[CH2:12][C:32]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:33])[C:23]=1[OH:24])[C:17]([O:19][CH3:20])=[O:18]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 0 °C
Procedure
To a solution of lithium bis(trimethylsilyl)amide (1.41 L, 1406 mmol) at −65° C. under nitrogen was added dropwise methyl 3-acetyl-5-bromo-4-hydroxybenzoate (120 g, 439 mmol) in THF (1.2 L). The solution was allowed to warm to 0° C., and maintained at this temperature for 1 hr. The solution was cooled back to −65° C. and morpholine-4-carbonyl chloride (0.055 L, 483 mmol) was added. The mixture was stirred at RT for 2 hrs then cooled to −30° C., DCM (1.5 L) and water (1 L) were added followed by dropwise addition of HCl 6N (500 mL) then HCl 2N (300 mL) until pH 7, the aqueous solution was extracted with DCM (3×). The combined extracts were dried over magnesium sulfate and evaporated. The crude product was triturated in MTBE to obtain methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate (153 g, 90%) as a beige solid. Mass Spectrum: M+H+ 388.
Workup
- temperaturemaintained at this temperature for 1 hr
- temperatureThe solution was cooled back to −65° C.
- temperaturethen cooled to −30° C.
- extractionHCl 2N (300 mL) until pH 7, the aqueous solution was extracted with DCM (3×)
- dry with materialThe combined extracts were dried over magnesium sulfate
- customevaporated
- customThe crude product was triturated in MTBE
Sources & evidence
- ORD record
- ord-3ea147c017cc49e5968242caf9fef9ea
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09029374B2
Reaction notes
Loading…