Trifluoromethanesulfonic acid → Methyl 4-amino-6-(1-fluoroethyl)-3-methoxypicolinate

HRID 407249Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([CH:8](O)[CH3:9])[N:5]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:3]=1[O:15][CH3:16].OS(C(F)(F)[F:22])(=O)=O.COCCN(S(F)(F)F)CCOC.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[NH2:1][C:2]1[CH:7]=[C:6]([CH:8]([F:22])[CH3:9])[N:5]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:3]=1[O:15][CH3:16]

Participants

Conditions

Temperature: -10 °C

Procedure

To a −10° C. (ice+NaCl) suspension of methyl 4-amino-6-(1-hydroxyethyl)-3-methoxypicolinate (0.3 g, 1.326 mmol) in Chloroform (6.63 ml) was added dropwise Triflic Acid (0.141 ml, 1.591 mmol) followed by Deoxo-Fluor® (0.257 ml, 1.392 mmol). The suspension was stirred at −10° C. (LC monitoring). After 2 h, the reaction mixture was poured into saturated NaHCO3 and extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified by flash column chromatography (ISCO, SiO2 24 g, hexane/EtOAc 100:0 to 0:100 gradient) to afford methyl 4-amino-6-(1-fluoroethyl)-3-methoxypicolinate (175 mg, 0.767 mmol, 57.8% yield) as a white solid. ESIMS m/z 227 ([M−H]−); 1H NMR (400 MHz, CDCl3) δ 6.91 (s, 1H), 5.59 (dq, J=47.6, 6.3 Hz, 1H), 4.53 (s, 2H), 3.97 (s, 3H), 3.87 (s, 3H), 1.62 (dd, J=24.6, 6.4 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −176.20.

Workup

extractionextracted with EtOAc (3×)
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash column chromatography (ISCO, SiO2 24 g, hexane/EtOAc 100:0 to 0:100 gradient)

Sources & evidence

ORD record: ord-1ca3c95972234489aa6f6d50bd4a1758
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754229B2

Reaction notes

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