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

HRID 1385091Notes

Reaction equation

HRID 1385091 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[CH:15]=[C:14]2[C:10]([C:11]([CH2:16][CH3:17])=[N:12][NH:13]2)=[CH:9][CH:8]=1)=[O:6].[CH:18]1(Br)[CH2:22][CH2:21][CH2:20][CH2:19]1.O>CN(C=O)C>[CH3:3][O:4][C:5]([C:7]1[CH:15]=[C:14]2[C:10]([C:11]([CH2:16][CH3:17])=[N:12][N:13]2[CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:9][CH:8]=1)=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 8728BromocyclopentaneHCID 24758Sodium hydrideHCID 178438014HCID 178438014, compound

Product 1

HCID 158960821-Cyclopentyl-3-ethyl-1H-indazole-6-carboxylic Acid Methyl EsterYield 72.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.17 g (29.4 mmol, 1.05 equiv) sodium hydride, 60% oil dispersion, were added in one portion to a room temperature solution of 5.7 g (27.9 mmol, 1.0 equiv) 3-ethyl-1H-indazole-6-carboxylic acid methyl ester in 125 mL anhydrous DMF. After 20 min., 3.89 mL (36.6 mmol, 1.3 equiv) cyclopentyl bromide were added dropwise, and the reaction mixture allowed to stir overnight at room temperature. The mixture was then poured into 1 L H2O and extracted 3×450 mL ethyl acetate. The organic extracts were combined, washed 3×400 mL H2O, 1×200 mL brine, and dried over Na2SO4. Filtration, concentration of filtrate and drying gave an amber oil, which was purified on a silica gel column (10% ethyl acetate/hexanes, gravity) to give 5.48 g (72%) of a clear oil: 1H NMR (300 MHz, CDCl3) δ 8.16 (d, 1H, J=1.0 Hz), 7.7 (m, 2H), 5.00 (quintet, 1H, J=7.5 Hz), 3.97 (s, 3H), 3.01 (q, 2H, J=7.6 Hz), 2.2 (m, 4H), 2.0 (m, 2H), 1.8 (m, 2H), 1.39 (t, 3H, J=7.6 Hz); HRMS calcd for C18H20N2O2272.1526. Found: 272.15078.

Workup

  1. extractionextracted 3×450 mL ethyl acetate
  2. washwashed 3×400 mL H2O, 1×200 mL brine
  3. dry with materialdried over Na2SO4
  4. filtrationFiltration, concentration of filtrate
  5. customdrying
  6. customgave an amber oil, which
  7. customwas purified on a silica gel column (10% ethyl acetate/hexanes, gravity)

Sources & evidence

ORD record
ord-9e83538ac3684e23a3ca54fed3637cde
Source dataset
uspto-grants-2001_07
Patent number
US06262040B1

Reaction notes

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