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

In a round-bottomed flask, 5,5-dimethyl-4,5,6,7-tetrahydro-1H-indazole (0.50 g, 3.33 mmol) was dissolved in DMF (7 mL). Iodine (1.69 g, 6.66 mmol) was added followed by potassium hydroxide (723 mg, 12.9 mmol). The dark reaction mixture was stirred at room temperature for 1.25 h. Additional iodine (1.69 g, 6.66 mmol) and potassium hydroxide (723 mg, 12.9 mmol) were added and the dark brown reaction mixture was stirred at room temperature for 1.5 h. The reaction was quenched with 10% aqueous NaHSO3 solution and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/Hexanes (gradient 0-20% EtOAc) to give 645 mg (70%) of 3-iodo-5,5-dimethyl-4,5,6,7-tetrahydro-1H-indazole as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 2.66 (t, J=6.6 Hz, 2H), 2.14 (s, 2H), 1.59 (t, J=6.4 Hz, 2H), 1.01 (s, 6H).

1. customThe dark reaction mixture
2. stirringthe dark brown reaction mixture was stirred at room temperature for 1.5 h
3. customThe reaction was quenched with 10% aqueous NaHSO3 solution
4. extractionextracted with diethyl ether (2×)
5. washThe combined organic layers were washed twice with water and once with brine
6. dry with materialthen dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was absorbed on silica gel
10. customchromatographed with EtOAc/Hexanes (gradient 0-20% EtOAc)

ORD record

ord-12ead5a87c54464588b5d5228e5b385f

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2