Phosgene → tert-Butyl (6-(chloromethyl)pyridin-2-yl)carbamate
Reaction equation
[C:1]([OH:5])([CH3:4])([CH3:3])[CH3:2].[C:6](Cl)(Cl)=[O:7].[NH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][Cl:18])[N:12]=1.C(N(CC)C(C)C)(C)C.[OH-].[Na+]>O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][Cl:18])[N:12]=1)([CH3:4])([CH3:3])[CH3:2]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Procedure
5.61 g (75.7 millimoles) of t-butanol and 22 mL of ethyl acetate were added to a reaction system followed by blowing in 3.8 g (38.4 millimoles) of phosgene. A mixed solution containing 1.95 g (13.7 millimoles) of 2-amino-6-chloromethylpyridine, 4.86 g (37.6 millimoles) of N,N-diisopropylethylamine and 19 mL of ethyl acetate were dropped into this solution over the course of 1 hour while holding the internal temperature at −15° C. to −5° C. Following completion of dropping, the solution was stirred for 1 hour. Next, water and 28% sodium hydroxide were sequentially added while holding the internal temperature at 0° C. or lower. After separating the liquid, the aqueous phase was extracted with ethyl acetate. The organic phases were combined and mixed. A portion of the organic phase was sampled and subjected to quantitative analysis by HPLC. The target (6-chloromethyl-pyridin-2-yl)-carbamic acid tert-butyl ester was obtained at yield of 74%. The yield of 1,3-bis-(6-chloromethyl-pyridin-2-yl)-urea (urea compound) was 10%.
Workup
- additionwere dropped into this solution over the course of 1 hour
- customat −15° C. to −5° C
- customat 0° C.
- customAfter separating the liquid
- extractionthe aqueous phase was extracted with ethyl acetate
- additionmixed
- aliquotA portion of the organic phase was sampled
Sources & evidence
- ORD record
- ord-e01cfbaf5bb7434c9e7ff89b3353057a
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08653269B2
Reaction notes
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