1,2-Dibromoethane → Methyl 1-(quinolin-6-yl)cyclopropanecarboxylate

HRID 456113Notes

Reaction equation

HRID 456113 reaction equation
[Li+].[CH3:2][CH:3]([N-]C(C)C)C.[CH3:9][O:10][C:11](=[O:23])[CH2:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][CH:17]=[CH:16]2.BrCCBr>C1COCC1>[CH3:9][O:10][C:11]([C:12]1([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[CH:18][CH:17]=[CH:16]3)[CH2:3][CH2:2]1)=[O:23]

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 1514202Methyl 6-quinolineacetateHCID 2724682Lithium diisopropylamide

Product 1

HCID 58190477Methyl 1-(quinolin-6-yl)cyclopropanecarboxylateYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of LDA (1.8 M solution in toluene, 14.8 ml, 26.6 mmol) was added dropwise to a solution of quinolin-6-yl-acetic acid methyl ester (2.14 g, 10.64 mmol) in dry THF (40 mL) under a nitrogen atmosphere at −78° C. After 30 min, 1,2-dibromoethane (2.40 g, 12.76 mmol) was added dropwise over 3 min. The resulting mixture was stirred for 1 h at room temperature, then quenched with satd aq. NH4Cl. The mixture was extracted with DCM, washed with brine, dried over Na2SO4, and stripped of solvent. The residue was purified by flash chromatography in silica gel eluting with a EtOAC/hexane gradient to afford 463 mg (20%) of the title compound as yellow solid. 1H-NMR (400 MHz, CDCl3) δ ppm 8.91 (dd, 1H), 8.12 (d, 1H), 8.07 (d, 1H), 7.77-7.74 (m, 2H), 7.40 (dd, 1H), 3.65 (s, 3H), 1.73-1.71 (m, 2H), 1.33-1.30 (m, 2H). LCMS (method A): [MH]+=228, tR=4.37 min.

Workup

  1. customquenched with satd aq. NH4Cl
  2. extractionThe mixture was extracted with DCM
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customThe residue was purified by flash chromatography in silica gel eluting with a EtOAC/hexane gradient

Sources & evidence

ORD record
ord-497dad94ce8749f68ddce116e9d12209
Source dataset
uspto-grants-2013_07
Patent number
US08497368B2

Reaction notes

Loading…