Ethyl Bromide → 2-Ethyl-6-methylisonicotinic acid

A solution of ethylmagnesiumbromide (freshly prepared from ethylbromide (392 mg, 3.6 mmol) and magnesium (83 mg, 3.4 mmol)) in Et2O (10 mL) is added to a cooled (−40° C.) and mechanically stirred solution of 2-chloro-6-methyl-isonicotinic acid tert-butyl ester (0.76 g, 3.34 mmol), Fe(acac)3 (21.2 mg, 0.06 mmol) and NMP (0.6 mL) in THF (60 mL). The mixture is warmed to r.t. during 0.5 h, diluted with Et2O (150 mL) and quenched with aq. KHSO4 (1 M, 40 mL). The phases are separated and the aq. phase is extracted with Et2O (2×50 mL). The combined organic extracts are dried (MgSO4), filtered and evaporated. The residue is purified by reversed phase MPLC. The obtained 2-ethyl-6-methyl-isonicotinic acid tert-butyl ester is dissolved in CH2Cl2 (10 mL). TFA (10 mL) is added and the mixture stirred at r.t. for 0.5 h. The mixture is evaporated and the residue dried in HV to provide the title compound.

1. additionis added to
2. customquenched with aq. KHSO4 (1 M, 40 mL)
3. customThe phases are separated
4. extractionthe aq. phase is extracted with Et2O (2×50 mL)
5. dry with materialThe combined organic extracts are dried (MgSO4)
6. filtrationfiltered
7. customevaporated
8. customThe residue is purified by reversed phase MPLC
9. dissolutionThe obtained 2-ethyl-6-methyl-isonicotinic acid tert-butyl ester is dissolved in CH2Cl2 (10 mL)
10. additionTFA (10 mL) is added
11. customThe mixture is evaporated
12. customthe residue dried in HV

ORD record

ord-7dfcbdeda1b84b53867644645d2767c6

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07750161B2