Bromocyclopentane → 1-Cyclopentyl-3-ethyl-1H-indazole-6-carboxylic Acid Methyl Ester

HRID 2240149Notes

Reaction equation

HRID 2240149 reaction equation
[H-].[Na+].C1OCCOCCOCCOCCOC1.[CH2:18]([C:20]1[C:28]2[C:23](=[CH:24][C:25]([C:29]([O:31][CH3:32])=[O:30])=[CH:26][CH:27]=2)[NH:22][N:21]=1)[CH3:19].[CH:33]1(Br)[CH2:37][CH2:36][CH2:35][CH2:34]1>C(OCC)(=O)C.CN(C=O)C>[CH:33]1([N:22]2[C:23]3[C:28](=[CH:27][CH:26]=[C:25]([C:29]([O:31][CH3:32])=[O:30])[CH:24]=3)[C:20]([CH2:18][CH3:19])=[N:21]2)[CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

7

Reactant 4

HCID 8728BromocyclopentaneHCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 178438014HCID 178438014, compound

Product 1

HCID 158960821-Cyclopentyl-3-ethyl-1H-indazole-6-carboxylic Acid Methyl Ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a flask containing 337 mg (8.4 mmol) of NaH (60% in mineral oil), 1.7 mL (8.4 mmol) of 15-crown-5 and 42 mL of DMF was added 860 mg (4.2 mmol) of methyl 3-ethyl-1H-indazol-6-yl-carboxylate. This mixture was stirred at room temperature for 3 hours and then 1.35 mL (12.6 mmol) of cyclopentyl bromide was added and the reaction was stirred at room temperature overnight. The solvent was removed and the residue was dissolved in 40 mL ethyl acetate, washed with 30 mL of water and 30 mL of brine, dried (Na2SO4), and concentrated. The residue was purified by column chromatography over SiO2 using a step gradient of 10% ethyl acetate in hexanes until the first compound eluted and then 50% ethyl acetate in hexanes to provide 662 mg (2.4 mmol) of methyl 1-cyclopentyl-3-ethyl-1H-indazol-6-yl-carboxylate as a clear oil along with 144 mg (0.53 mmol) methyl 2-(cyclopentyl-3-ethyl)-2H-indazol-6-yl-carboxylate as a yellow oil. 1H-NMR (CDCl3) δ 8.17 (s, 1H), 7.71 (dd, J1=8.4 Hz, J2=6.7 Hz, 2H), 5.0 (p, J=7.5 Hz, 1H), 3.97 (s, 3H), 3.00 (q, J=7.5 Hz, 2H), 2.16 (m, 4H), 1.92 (m, 2H), 1.74 (m, 2H), 1.39 (t, J=7.6 Hz, 3H).

Workup

  1. stirringthe reaction was stirred at room temperature overnight
  2. customThe solvent was removed
  3. dissolutionthe residue was dissolved in 40 mL ethyl acetate
  4. washwashed with 30 mL of water and 30 mL of brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography over SiO2 using a step gradient of 10% ethyl acetate in hexanes until the first compound
  8. washeluted

Sources & evidence

ORD record
ord-eca63a05c9cb44a28300f5ba6a52fb8a
Source dataset
uspto-grants-2010_05
Patent number
US07723348B2

Reaction notes

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