5-Amino-2-fluoropyridine → (2S,4S)-Benzyl 2-(6-fluoropyridin-3-ylcarbamoyl)-4-methoxypyrrolidine-1-carboxylate
Reaction equation
[F:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[CH3:14][O:15][C@@H:16]1[CH2:20][N:19]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[C@H:18]([C:31](OC)=[O:32])[CH2:17]1>C1COCC1>[F:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:31]([C@@H:18]2[CH2:17][C@H:16]([O:15][CH3:14])[CH2:20][N:19]2[C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])=[O:32])=[CH:4][CH:3]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 6-fluoropyridin-3-amine (500 mg, 4.46 mmol) in THF (15 mL) was added isopropylmagnesium chloride (2.0 M THF solution, 2.12 mL, 4.24 mmol) dropwise at 0° C. The resulting reaction mixture was stirred at room temperature for 30 min. A solution of (2S,4S)-1-benzyl 2-methyl 4-methoxypyrrolidine-1,2-dicarboxylate 18B (435 mg, 1.49 mmol) in THF (2 mL) was added to the reaction mixture. The reaction mixture was stirred at room temperature for 4 h and quenched with methanol (3 mL). The crude product was purified by prep. HPLC to give (2S,4S)-benzyl 4-methoxy-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylate 62A (424 mg, 80%) as an oil. LC/MS [M+H-Boc]+: 240; Ret time (Method F): 2.43 min.
Workup
- customThe resulting reaction mixture
- stirringThe reaction mixture was stirred at room temperature for 4 h
- customquenched with methanol (3 mL)
- customThe crude product was purified by prep
Sources & evidence
- ORD record
- ord-af7dee00ec8f46c884886c7cad1848c5
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415340B2
Reaction notes
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