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

HRID 1892404Notes

Reaction equation

HRID 1892404 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>[N:19]1[C:20]2[C:15](=[CH:14][C:13]([C:12]3([C:11]([O:10][CH3:9])=[O:23])[CH2:3][CH2:2]3)=[CH:22][CH:21]=2)[CH:16]=[CH:17][CH:18]=1

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

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 nitrogen 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 rt, then quenched with saturated aqueous NH4Cl, extracted with DCM, washed with brine, dried over Na2SO4, and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with EtOAc/hexane gradient to afford the title compound as a yellow solid (463 mg, 20%). 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 saturated aqueous NH4Cl
  2. extractionextracted with DCM
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel eluting with EtOAc/hexane gradient

Sources & evidence

ORD record
ord-c437f11fab0c4970a2e74fb30a8f4e68
Source dataset
uspto-grants-2013_08
Patent number
US08507676B2

Reaction notes

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