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

HRID 243551Notes

Reaction equation

HRID 243551 reaction equation
[C:1](Cl)(Cl)=[O:2].[NH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[N:7]=1.C(N(CC)CC)C.[C:20]([OH:24])([CH3:23])([CH3:22])[CH3:21]>ClC1C=CC=CC=1.O>[C:20]([O:24][C:1](=[O:2])[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[N:7]=1)([CH3:23])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 6371Phosgene2×HCID 6386tert-ButanolHCID 8471Triethylamine2×HCID 157652-Amino-6-methylpyridine

Product 1

HCID 11367776tert-Butyl (6-methylpyridin-2-yl)carbamateYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7964ChlorobenzeneSolvent3×

Procedure

556.0 g (500 mL) of monochlorobenzene were added to a reaction system followed by blowing in 107.8 g (1.09 moles) of phosgene over the course of 1 hour at −10° C. to −5° C. A mixed solution containing 54.07 g (0.5 moles) of 2-amino-6-picoline, 107 g (1.06 moles) of triethylamine, 92.7 g (1.25 moles) of t-butanol and 333 g (300 mL) of monochlorobenzene were dropped into this phosgene solution over the course of 4.5 hours while holding the internal temperature at −11° C. to −8° C. Following completion of dropping, the solution was stirred for 0.5 hours. Next, a mixed solution obtained by dissolving 120 g (1.19 moles) of triethylamine in 217.4 g (200 mL) of monochlorobenzene was dropped in over the course of 1 hour while holding the internal temperature at −10° C. to −5° C. Following completion of dropping, the solution was stirred for 0.2 hours. Next, 300 mL of water were added. The organic phase was washed with 150 mL of water. The organic phase was subjected to quantitative analysis by HPLC. The target (6-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester was obtained at a yield of 92%. The yield of 1,3-bis-(6-methyl-pyridin-2-yl)-urea (urea compound) was 4%. 4% of the 2-amino-6-picoline used for the starting material remained.

Workup

  1. customat −11° C. to −8° C
  2. customNext, a mixed solution obtained
  3. additionwas dropped in over the course of 1 hour
  4. customat −10° C. to −5° C
  5. stirringthe solution was stirred for 0.2 hours
  6. washThe organic phase was washed with 150 mL of water

Sources & evidence

ORD record
ord-b2f6f3b5304c49328b62b1c4993b82fe
Source dataset
uspto-grants-2014_02
Patent number
US08653269B2

Reaction notes

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