Hydrochloric Acid → (6-Morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-carbamic acid methyl ester

HRID 1017491Notes

Reaction equation

HRID 1017491 reaction equation
[CH3:1][O-:2].[Na+].Br[N:5]1[C:9](=[O:10])CCC1=O.[N:12]1([C:18]2[CH:26]=[C:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH3:33])[C:21](C(N)=O)=[CH:20][N:19]=2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.Cl>ClCCl>[CH3:1][O:2][C:9](=[O:10])[NH:5][C:21]1[CH:20]=[N:19][C:18]([N:12]2[CH2:13][CH2:14][O:15][CH2:16][CH2:17]2)=[CH:26][C:25]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH3:33]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 67184N-bromobutanimideHCID 10942334Sodium MethoxideHCID 111622966-Morpholin-4-yl-4-o-tolyl-nicotinamide

Product 1

HCID 12167319(6-Morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-carbamic acid methyl esterYield 74.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-5 °C

Procedure

9.9 ml (53.7 mMol) Sodium methoxide solution (5.4 M in MeOH) were added over 15 minutes to a solution of 3.9 g (21.5 mMol) N-bromosuccinimide in 22.5 ml dichloromethane cooled to −5° C. The milky suspension was stirred at −5° C. for 18 hours, then, at the same temperature, a solution of 4.5 g (14 mMol) 6-morpholin-4-yl-4-o-tolyl-nicotinamide in 22.5 ml dichloromethane was added over 15 minutes. After 5 hours at 5° C., 33 ml (33 mMol) aqueous HCl 1N were added, the phases were separated, the organic phase washed with water and the aqueous phases extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and evaporated. The residue was treated with basic Alox (1:1 weight) in ethyl acetate/heptane 1:1 for 30 minutes at room temperature. After filtration and removal of the solvents, the residue was crystallized from di-iso-propylether/n-heptane 1:2 at 0° C. to yield 3.4 g (72.5%) (6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-carbamic acid methyl ester as a yellow powder.

Workup

  1. waitAfter 5 hours at 5° C.
  2. customthe phases were separated
  3. washthe organic phase washed with water
  4. extractionthe aqueous phases extracted with dichloromethane
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. customevaporated
  7. additionThe residue was treated with basic Alox (1:1 weight) in ethyl acetate/heptane 1:1 for 30 minutes at room temperature
  8. filtrationAfter filtration and removal of the solvents
  9. customthe residue was crystallized from di-iso-propylether/n-heptane 1:2 at 0° C.

Sources & evidence

ORD record
ord-68b47aaa1c644a18a4992075ff852076
Source dataset
uspto-grants-2002_11
Patent number
US06479483B2

Reaction notes

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