Iodine → 3-Iodo-4,5,6,7-tetrahydro-1H-indazole

HRID 246404Notes

Reaction equation

[NH:1]1[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[C:3](C(O)=O)=[N:2]1.C(=O)(O)[O-].[Na+].[I-:18].[Na+].II>ClC(Cl)C.O.ClCCl>[I:18][C:3]1[C:4]2[CH2:5][CH2:6][CH2:7][CH2:8][C:9]=2[NH:1][N:2]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid (0.57 g, 3.43 mmol), and sodium bicarbonate (951 mg, 440 μL, 11.3 mmol) in dichloroethane (5 mL) and water (5 mL) were added in one portion sodium iodide (1.34 g, 8.92 mmol) and iodine (1.13 g, 4.46 mmol) and the mixture heated at to 100° C. (oil bath temperature) with vigorous stirring for 24 h. After cooling to 25° C. the mixture was diluted with dichloromethane, then washed with 10% Na2S2O3 and saturated NaHCO3. The organic phases were combined, dried (MgSO4) and concentrated to an off-white solid which was purified by chromatography (115 g column, 50 μm from Analogix, 0 to 5% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane to give 3-iodo-4,5,6,7-tetrahydro-1H-indazole (674 mg, 2.72 mmol, 79.2%) as a white solid. MS (M+H)+=249 (>90% purity); 1H NMR (CDCl3) δ: 2.75 (t, J=5.7 Hz, 2H), 2.35 (t, J=5.7 Hz, 2H), 1.61-1.90 (m, 4H).

Workup

temperatureAfter cooling to 25° C. the mixture
washwashed with 10% Na2S2O3 and saturated NaHCO3
dry with materialdried (MgSO4)
concentrationconcentrated to an off-white solid which
customwas purified by chromatography (115 g column, 50 μm from Analogix, 0 to 5% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane

Sources & evidence

ORD record: ord-7c9f1b094b114b7496522b6c6007a384
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

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