4-Chlorobenzoyl chloride → methyl 2-(1-(4-chlorobenzoyl)-1H-indazol-3-yl)acetate

HRID 527456Notes

Reaction equation

HRID 527456 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([O:13][CH3:14])=[O:12])=[N:2]1.CC([O-])(C)C.[Na+].[Cl:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][CH:23]=1>C1COCC1>[Cl:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]([CH2:10][C:11]([O:13][CH3:14])=[O:12])=[N:2]2)=[O:27])=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 85014-Chlorobenzoyl chlorideHCID 23676156Sodium t-butoxideHCID 178499646HCID 178499646, compound

Product 1

HCID 89514728methyl 2-(1-(4-chlorobenzoyl)-1H-indazol-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled solution (ice bath, 0-5° C.) of methyl 2-(1H-indazol-3-yl)acetate (80 mg, 0.42 mmol) in THF (2.5 mL) was added tBuONa (2 M in THF, 252.4 μL, 0.50 mmol), and the mixture was stirred for 25 min at the low temperature. 4-Chlorobenzoyl chloride (88.3 mg, 0.50 mmol) was added and the reaction was aged overnight at room temperature. The reaction was quenched with saturated aqueous NH4Cl (provided in a commercial phase separator syringe) and the organic compound was extracted with CH2Cl2, washed with brine and water, dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was subjected to flash chromatography (SiO2, ethyl acetate/hexane gradient) to afford the title compound as yellow oil, which permanently crystallized upon drying at high vacuum and storage at −20° C. Yield: 51 mg (37%). C17H13ClN2O3, Mr=328.75; 1H NMR (400 MHz, DMSO-d6) d: 3.65 (s, 3H), 4.16 (s, 2H), 7.50 (td, J=0.8/7.6 Hz, 1H), 7.63-7.66 (m, 2H), 7.71 (td, J=1.0/7.6 Hz, 1H), 7.91 (d, J=8.0 Hz, 1H), 8.00-8.03 (m, 2H), 8.41 (d, J=8.4 Hz, 1H); LCMS (ESI) tR: 2.80 min (>99%, ELSD), m/z: 329.0 [M+1]+.

Workup

  1. waitthe reaction was aged overnight at room temperature
  2. customThe reaction was quenched with saturated aqueous NH4Cl (provided in a commercial phase separator syringe)
  3. extractionthe organic compound was extracted with CH2Cl2
  4. washwashed with brine and water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fd1690c64c024e6499f49a8fbcdd8195
Source dataset
uspto-grants-2016_05
Patent number
US09346803B2

Reaction notes

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