Di-tert-butyl dicarbonate → Tert-butyl (6-bromopyridin-2-YL)carbamate
Reaction equation
[Br:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[O:9](C(OC(C)(C)C)=O)[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:10](=[O:9])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[CH:4][CH:3]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 6-bromopyridin-2-amine (15 g, 86.49 mmol, 1 eq.) in 250 ml of DCM cooled to 0° C. were added DMAP (1.05 g, 8.67 mmol, 0.1 eq.), TEA (9.65 g, 95.36 mmol, 1.1 eq.) and BOC2O (22.70 g, 104.03 mmol, 1.2 eq.) portionwise. The reaction was stirred at 0° C. for 5 h and quenched with sat. aqueous NH4Cl. The aqueous layer was extracted with DCM, and the organics were combined, dried over MgSO4 and concentrated. The crude residue was purified by chromatography on silica gel to give impure tert-butyl (6-bromopyridin-2-yl)carbamate (mix 80/20 of mono and bis BOC) as a white solid. A chemical purification was then done. This solid was dissolved in 250 ml of THF cooled to 0° C. then iPrMgCl.LiCl (2 M, 51.89 ml, 103.78 mmol, 1.2 eq.) was added dropwise. The solution was stirred 30 min and quenched with aqueous sat. NH4Cl. The aqueous layer was separated and extracted with DCM. The organics were combined, dried over MgSO4 and concentrated to give tert-butyl (6-bromopyridin-2-yl)carbamate (15.96 g, 68%) as a white solid.
Workup
- customquenched with sat. aqueous NH4Cl
- extractionThe aqueous layer was extracted with DCM
- dry with materialdried over MgSO4
- concentrationconcentrated
- customThe crude residue was purified by chromatography on silica gel
Sources & evidence
- ORD record
- ord-b056ec74355d49c588b2300ccc12ea3b
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08466176B2
Reaction notes
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