Ethanol → HCID 178502673, compound

HRID 1670523Notes

Reaction equation

HRID 1670523 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][N:3]=1.Cl.[CH3:12][NH:13][O:14][CH3:15].C(O)C.N1C=CC=CC=1>[Cl-].[Na+].O>[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:13]([O:14][CH3:15])[CH3:12])=[O:7])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 1049PyridineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 178521114HCID 178521114, compound

Product 1

HCID 178502673HCID 178502673, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Add 6-hydroxy-nicotinoyl chloride (11.2 g, 71 mmol) and N,O-dimethylhydroxylamine hydrochloride (7.76 g, 79.5 mmol) to ethanol-free chloroform (100 mL, wash chloroform with water, dry over MgSO4, then filter through neutral alumina to obtain ethanol-free chloroform). Cool the mixture to 0° C. under a nitrogen atmosphere. Add pyridine (12.6 mL, 155.8 mmol), warm reaction up to room temperature and stir for 16 h under a nitrogen atmosphere. Wash reaction with water (2×75 mL) followed by brine (75 mL). Dry the organic layer over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with DCM/2M ammonia in methanol (44:1) to obtain the desired intermediate as a yellow solid (8.6 g, 67%). MS (ES+) m/z: 183.2 (M+H)+.

Workup

  1. washwash chloroform with water
  2. dry with materialdry over MgSO4
  3. filtrationfilter through neutral alumina
  4. customto obtain ethanol-free chloroform)
  5. customreaction up to room temperature
  6. washWash
  7. customreaction with water (2×75 mL)
  8. dry with materialDry the organic layer over MgSO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customPurify the crude mixture by chromatography on silica gel eluting with DCM/2M ammonia in methanol (44:1)

Sources & evidence

ORD record
ord-abb457caeab048309e9fb3da14ffcc83
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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