Benzonitrile, m-chloro- → Methyl 2-(2-chloro-4-cyanophenyl)acetate

HRID 76865

Reaction equation

HRID 76865 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:20]([C:22]([O:24][CH3:25])=[O:23])#N>C1COCC1>[CH3:25][O:24][C:22](=[O:23])[CH2:20][C:9]1[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=1[Cl:1]

Participants

5

Reactant 3

HCID 13015Benzonitrile, m-chloro-HCID 28660Carbonocyanidic acid, methyl esterHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 86611068Methyl 2-(2-chloro-4-cyanophenyl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-{5-[2-tert-Butyldimethylsilanyloxy)ethyl]imidazol-1-ylmethyl}-3-chlorobenzonitrile (1.7 g, 4.52 mmol) is dissolved in anhydrous THF (30 mL) and stirred at −78° C. before a THF solution of LHMDS (8.1 mL, 1.0 M) is added. After 15 min, methyl cyanoformate (0.38 mL, 4.74 mmol) is added and the solution is left at −78° C. for 2 h. The excess LHMDS is quenched with aqueous saturated NH4Cl and the mixture is allowed to warm to room temperature. The mixture is then diluted with EtOAc and washed with aqueous saturated NH4Cl (2×). Organic is dried (Na2SO4) and evaporated. The crude residue is purified via flash column chromatography (EtOAc/hexanes 1:1→EtOAc) to give {5-[2-tert-butyldimethylsilanyloxy)ethyl]-imidazol-1-yl}-(2-chloro-4-cyanophenyl)acetic acid methyl ester as an oil. MS (ESI) m/z 434.3, 436.3 (M+H).

Workup

  1. additionis added
  2. waitthe solution is left at −78° C. for 2 h
  3. customThe excess LHMDS is quenched with aqueous saturated NH4Cl
  4. additionThe mixture is then diluted with EtOAc
  5. washwashed with aqueous saturated NH4Cl (2×)
  6. dry with materialOrganic is dried (Na2SO4)
  7. customevaporated
  8. customThe crude residue is purified via flash column chromatography (EtOAc/hexanes 1:1→EtOAc)

Sources & evidence

ORD record
ord-dfb441574fa942208fb18e6416ac21d7
Source dataset
uspto-grants-2014_09
Patent number
US08835646B2

Linked notes

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