Phosgene → tert-Butyl (6-methylpyridin-2-yl)carbamate

HRID 243544Notes

Reaction equation

HRID 243544 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]([CH3:17])[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]([CH3:17])[N:12]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 6371PhosgeneHCID 6386tert-ButanolHCID 14798Sodium HydroxideHCID 157652-Amino-6-methylpyridineHCID 81531Diisopropylethylamine

Product 1

HCID 11367776tert-Butyl (6-methylpyridin-2-yl)carbamateYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

14.8 g (200 millimoles) of t-butanol and 29 ml of ethyl acetate were added to a reaction system followed by blowing in 9.9 g (100 millimoles) of phosgene. A mixed solution containing 5.48 g (50.7 millimoles) of 2-amino-6-picoline, 12.5 g (97.0 millimoles) of N,N-diisopropylethylamine and 32 mL of ethyl acetate was dropped into this solution over the course of 1.5 hours while holding the internal temperature at −15° C. to −5° C. Following completion of dropping, the solution was stirred for 1 hour. Next, 50 mL of water and 5.1 g of 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, and a portion of the organic phase was sampled and subjected to quantitative analysis by HPLC. The target (6-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester was obtained at a yield of 89%. The yield of 1,3-bis-(6-methyl-pyridin-2-yl)-urea (urea compound) was 8%. Furthermore, the yield of the urea compound was based on the raw material 2-amino-6-picoline and was calculated using 2 molecules of 2-amino-6-picoline for 1 molecule of the urea compound (and was similarly calculated in the subsequent examples and comparative examples).

Workup

  1. additionwas dropped into this solution over the course of 1.5 hours
  2. customat −15° C. to −5° C
  3. customat 0° C.
  4. customAfter separating the liquid
  5. extractionthe aqueous phase was extracted with ethyl acetate
  6. additionmixed
  7. aliquota portion of the organic phase was sampled

Sources & evidence

ORD record
ord-246f34ca3ed245adaa51cc39d4f75a7d
Source dataset
uspto-grants-2014_02
Patent number
US08653269B2

Reaction notes

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