1,2-Dichloroethane → 2-Chloro-N-methoxy-N-methylisonicotinamide

HRID 1355475Notes

Reaction equation

HRID 1355475 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([NH:7][CH3:8])=[O:6].Cl.CN[O:15][CH3:16].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([N:7]([O:15][CH3:16])[CH3:8])=[O:6]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 151158492-chloro-N-methylisonicotinamide

Product 1

HCID 185068942-Chloro-N-methoxy-N-methylisonicotinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-Chloroisonicotinic acid (12-2, 2.0 g, 12.7 mmole), N,O-dimethylhydroxylamine hydrochloride (3.71 g, 38.1 mmole), EDC (2.92 g, 15.2 mmole), and HOBt (2.06 g, 15.2 mmole) were combined in dry DMF (40 mL). To this was added Et3N (8.9 mL, 63.47 mmole) at RT. After 60 hr the mixture was diluted with H2O and extracted with EtOAc (4×). The combined organic layers were washed with H2O, brine; then dried (MgSO4), filtered, and concentrated to give the titled compound as an amber oil which solidified on standing. The material was sufficiently pure for use in the next step. 1H-NMR (500 MHz, CDCl3) δ8.47 (d, 1H, J=5.13 Hz), 7.57 (s, 1H), 7.45 (m, 1H), 3.56 (s, 3H), 3.38 (s, 3H).

Workup

  1. extractionextracted with EtOAc (4×)
  2. washThe combined organic layers were washed with H2O, brine
  3. dry with materialthen dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-591fbf8ee587406b9e718c5d311af1ce
Source dataset
uspto-grants-2003_07
Patent number
US06586423B2

Reaction notes

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