Hydrochloric Acid → HCID 71150575, compound

HRID 407252Notes

Reaction equation

HRID 407252 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[CH3:9])[N:5]=[C:4]([C:12]([O:14]C)=[O:13])[C:3]=1[O:16][CH3:17].[OH-].[Na+].Cl>C1COCC1.CO>[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:11])[CH3:9])[N:5]=[C:4]([C:12]([OH:14])=[O:13])[C:3]=1[O:16][CH3:17]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 71150657HCID 71150657, compound

Product 1

HCID 71150575HCID 71150575, compoundYield 87.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-amino-6-(1,1-difluoroethyl)-3-methoxypicolinate (0.229 g, 0.930 mmol) in THF (2.325 ml) and MeOH (2.325 ml) was added a 2 N solution of sodium hydroxide (1.395 ml, 2.79 mmol). The reaction mixture was stirred at room temperature (LC monitoring). After 4 h, the reaction mixture was acidified with a 2 N solution of HCl (2 mL) and then concentrated (rotavap). The resulting white solid was dissolved into DMF and a few drops of water and was purified by preparative HPLC (reverse phase, C18 column) to afford 4-amino-6-(1,1-difluoroethyl)-3-methoxypicolinic acid (188 mg, 0.810 mmol, 87% yield) as an orange oil. EIMS m/z 208; 1H NMR (400 MHz, CDCl3) δ 6.86 (s, 1H), 6.71 (dd, J=17.6, 10.9 Hz, 1H), 5.98 (dd, J=17.6, 1.0 Hz, 1H), 5.42 (dd, J=10.9, 1.0 Hz, 1H), 4.45 (s, 2H), 3.97 (s, 3H), 3.87 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 165.94, 152.06, 148.02, 143.34, 141.60, 136.73, 118.02, 108.63, 61.49, 52.84.

Workup

  1. concentrationconcentrated (rotavap)
  2. dissolutionThe resulting white solid was dissolved into DMF and a few drops of water
  3. customwas purified by preparative HPLC (reverse phase, C18 column)

Sources & evidence

ORD record
ord-70835df4da68446a9ab2f56e6a73228e
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

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