Ethyl Bromide → 2-Ethyl-6-methylisonicotinic acid tert-butyl ester

HRID 2366117Notes

Reaction equation

HRID 2366117 reaction equation
[CH2:1]([Mg]Br)[CH3:2].C(Br)C.[Mg].[C:9]([O:13][C:14](=[O:23])[C:15]1[CH:20]=[C:19]([CH3:21])[N:18]=[C:17](Cl)[CH:16]=1)([CH3:12])([CH3:11])[CH3:10]>CCOCC.C1COCC1.CN1C(=O)CCC1>[C:9]([O:13][C:14](=[O:23])[C:15]1[CH:20]=[C:19]([CH3:21])[N:18]=[C:17]([CH2:1][CH3:2])[CH:16]=1)([CH3:12])([CH3:11])[CH3:10]

Participants

8

Reactant 4

HCID 6332Ethyl BromideHCID 5462224MagnesiumHCID 860403662-Chloro-6-methyl-isonicotinic acid tert-butyl esterHCID 178418443HCID 178418443, compound

Product 1

HCID 670269672-Ethyl-6-methylisonicotinic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

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 rt 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 to give 2-ethyl-6-methyl-isonicotinic acid tert-butyl ester; LC-MS: tR=0.67 min, [M+1]+=222.19; 1H NMR (CDCl3): δ 7.44 (s, 2 H), 2.83 (q, J=7.6 Hz, 2 H), 2.58 (s, 3 H), 1.59 (s, 9 H), 1.30 (t, J=7.6 Hz, 3 H).

Workup

  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

Sources & evidence

ORD record
ord-151ead3be97f4853973846455502f25d
Source dataset
uspto-grants-2014_04
Patent number
US08697732B2

Reaction notes

Loading…