Diisopropylamine → Ethyl 8-bromo-4-oxo-2-(3-(trifluoromethyl)phenyl)-1,4-dihydro-1,6-naphthyridine-3-carboxylate
Reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[Br:19][C:20]1[C:25]2[N:26]=[C:27]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)[O:28][C:29](=O)[C:24]=2[CH:23]=[N:22][CH:21]=1.[OH-].[Na+]>[Cl-].[Na+].O.C1COCC1>[Br:19][C:20]1[CH:21]=[N:22][CH:23]=[C:24]2[C:25]=1[NH:26][C:27]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:38])([F:40])[F:39])[CH:32]=1)=[C:14]([C:13]([O:16][CH2:17][CH3:18])=[O:15])[C:29]2=[O:28]Participants
8
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -78 °C
Procedure
A mixture of THF (15 mL) and diisopropylamine (1.40 mL, 10.0 mmol) was cooled to −78° C., and n-BuLi (4.0 mL, 2.5 M in hexanes, 10.0 mmol) was added. After stirring at −78° C. for 20 min, ethyl acetate (1.0 L, 10.2 mmol) was added and stirring was continued for 5 min. 8-bromo-2-(3-(trifluoromethyl)phenyl)-4H-pyrido[4,3-d][1,3]oxazin-4-one 47 (990 mg, 2.67 mmol) was added. After 1 h, the reaction mixture was gradually warmed to room temperature. 1N NaOH (15 mL) was added and the reaction mixture was stirred for 24 h. The mixture was poured into brine (50 mL), extracted with ethyl acetate (2×50 mL), dried (MgSO4), and concentrated in vacuo. The resulting solid was purified by MPLC to give 48 (910 mg, 77% yield).
Workup
- stirringstirring
- waitwas continued for 5 min
- waitAfter 1 h
- temperaturethe reaction mixture was gradually warmed to room temperature
- stirringthe reaction mixture was stirred for 24 h
- extractionextracted with ethyl acetate (2×50 mL)
- dry with materialdried (MgSO4)
- concentrationconcentrated in vacuo
- customThe resulting solid was purified by MPLC
Sources & evidence
- ORD record
- ord-a10695db03d04960b1023d3de8286f7b
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09326986B2
Reaction notes
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