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

HRID 1924822

Reaction equation

HRID 1924822 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, 2H), 2.83 (q, J=7.6 Hz, 2H), 2.58 (s, 3H), 1.59 (s, 9H), 1.30 (t, J=7.6 Hz, 3H).

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-c9aaad0c9712469f92d29d775a73a557
Source dataset
uspto-grants-2012_05
Patent number
US08178562B2

Linked notes

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