HCID 178418368, compound → HCID 178446955, compound

HRID 1670524Notes

Reaction equation

HRID 1670524 reaction equation
[OH:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](N(OC)C)=[O:7])=[CH:4][N:3]=1.[CH2:14]([Mg]Cl)[CH:15]([CH3:17])[CH3:16]>C1COCC1>[OH:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](=[O:7])[CH2:14][CH:15]([CH3:17])[CH3:16])=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 178418368HCID 178418368, compoundHCID 178502673HCID 178502673, compound

Product 1

HCID 178446955HCID 178446955, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 6-hydroxy-N-methoxy-N-methyl-nicotinamide (1.89 g, 10.4 mmol) in anhydrous THF (40 mL), then cool the solution to 0° C. Add isobutyl magnesium chloride (16 mL, 32 mmol, 2M solution in diethyl ether) under nitrogen, allow the mixture to warm gradually to room temperature and then stir for 16 h. Quench the reaction with 1M aqueous HCl and concentrate the mixture in vacuo. Extract the aqueous mixture with EtOAc (4×50 mL). Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo to obtain a yellow solid. Purify by chromatography on silica gel eluting with DCM/2M ammonia in methanol (23:2) to obtain the desired intermediate as a white solid (1.28 g, 69%). MS (ES+) m/z: 180.2 (M+H)+.

Workup

  1. temperatureto warm gradually to room temperature
  2. customQuench
  3. customthe reaction with 1M aqueous HCl
  4. concentrationconcentrate the mixture in vacuo
  5. extractionExtract the aqueous mixture with EtOAc (4×50 mL)
  6. dry with materialDry the combined organic extracts over MgSO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customto obtain a yellow solid
  10. customPurify by chromatography on silica gel eluting with DCM/2M ammonia in methanol (23:2)

Sources & evidence

ORD record
ord-e3353fdd09e14015a63efa7e54376fac
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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