Methanol → N-tert.-butyl-6-chloro-4-(prop-2-yl)-nicotinamide

HRID 379435Notes

Reaction equation

HRID 379435 reaction equation
[CH:1]([Mg]Cl)([CH3:3])[CH3:2].[C:6]([NH:10][C:11](=[O:19])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[N:14][CH:13]=1)([CH3:9])([CH3:8])[CH3:7].CO.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1COCC1>[C:6]([NH:10][C:11](=[O:19])[C:12]1[C:17]([CH:1]([CH3:3])[CH3:2])=[CH:16][C:15]([Cl:18])=[N:14][CH:13]=1)([CH3:9])([CH3:7])[CH3:8]

Participants

6

Reactant 4

HCID 887MethanolHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 11816697N-tert-butyl-6-chloronicotinamideHCID 178418918HCID 178418918, compound

Product 1

HCID 11414149N-tert.-butyl-6-chloro-4-(prop-2-yl)-nicotinamideYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

7.0 ml (14.1 mMol) iso-Propylmagnesium chloride solution (2M in THF) were added over 5 minutes to a solution of 1.0 g (4.7 mMol) N-tert.-butyl-6-chloro-nicotinamide in 5.0 ml THF cooled to 0° C. and the reaction mixture was stirred 18 hours at room temperature. After cooling to 0° C., 1.14 ml (28.2 mMol) methanol were added over 10 minutes, followed, after 15 minutes, by 1.17 g (5.2 mMol) 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. After stirring 30 minutes at room temperature, the red-brown solution was concentrated under reduced pressure to about 10 g, heated to 50° C. and 20 ml tert.-butyl-methylether were added. The resulting suspension was stirred 1 hour at 55° C., then 1 hour at room temperature and filtered. The filtrate was concentrated under reduced pressure and digested in 9 ml n-hexane/ethyl acetate 4:1 to yield 0.67 g (56%) N-tert.-butyl-6-chloro-4-(prop-2-yl)-nicotinamide as a beige powder of m.p.=130-140° C. (dec.)

Workup

  1. temperatureAfter cooling to 0° C.
  2. stirringAfter stirring 30 minutes at room temperature
  3. concentrationthe red-brown solution was concentrated under reduced pressure to about 10 g
  4. temperatureheated to 50° C.
  5. addition20 ml tert.-butyl-methylether were added
  6. stirringThe resulting suspension was stirred 1 hour at 55° C.
  7. filtration1 hour at room temperature and filtered
  8. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-3365bc037e9f42cc9a32c83156492df0
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

Loading…