Formic Acid → HCID 11846679, compound

HRID 1037263Notes

Reaction equation

HRID 1037263 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([NH2:11])=[C:6]([N+:12]([O-])=O)[C:5]=1[O:15][CH3:16].O.O.[Sn](Cl)Cl.O.[OH-].[Na+].[CH:26](O)=O>>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]([Cl:10])[C:7]2[N:11]=[CH:26][NH:12][C:6]=2[C:5]=1[O:15][CH3:16])=[O:17]

Participants

6

Reactant 5

HCID 284Formic AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 61436Stannous chloride dihydrateHCID 12097752Methyl 4-amino-5-chloro-2-methoxy-3-nitrobenzoate

Product 1

HCID 11846679HCID 11846679, compoundYield 31%

Conditions

Temperature
130 °C

Procedure

To a solution of 4-amino-5-chloro-2-methoxy-3-nitro-benzoic acid methyl ester (1.00 g, 3.84 mmol, prepared as described in J. Med. Chem., 2006, 49, 4762-4766) in formic acid (10.5 mL), was added tin(II) chloride dihydrate (2.6 g, 11.5 mmol). The reaction mixture was heated at 130° C. in the microwave for 10 min. Upon cooling to RT, water was added (50 mL) and the pH of the resultant mixture was adjusted to ˜7 by careful addition of 5 M sodium hydroxide. The resultant mixture was filtered through a Celite® and sand filter cake, washing with EtOAc (5×30 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 100% EtOAc in pentane) to afford the title compound as an off-white solid (0.29 g, 31%). LCMS (Method A): RT=3.40 min, [M+H]+=241/243.

Workup

  1. temperatureUpon cooling to RT
  2. filtrationThe resultant mixture was filtered through a Celite® and sand
  3. filtrationfilter cake
  4. washwashing with EtOAc (5×30 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7238e0147ae7488bba71d1bf4b404072
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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