Methyl iodide → 3-iodo-1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazole

HRID 245975Notes

Reaction equation

[I:1][C:2]1[C:10]2[CH2:9][CH2:8][C:7]([CH3:12])([CH3:11])[CH2:6][C:5]=2[NH:4][N:3]=1.[CH3:13]C([O-])(C)C.[K+].IC>C1COCC1>[I:1][C:2]1[C:10]2[CH2:9][CH2:8][C:7]([CH3:12])([CH3:11])[CH2:6][C:5]=2[N:4]([CH3:13])[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-iodo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazole (919 mg, 3.33 mmol) in THF (8 mL) at 0° C. was added KOt-Bu (523 mg, 4.66 mmol). The reaction mixture was stirred at 0° C. for 30 min then iodomethane (0.29 mL, 4.66 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min then warmed to room temperature and stirred for 1.5 h. The reaction was quenched with water and extracted with EtOAc (2×). The combined organics were dried over MgSO4 and concentrated. The residue was absorbed onto SiO2 and purified by chromatography with 10% to 20% EtOAc/hexanes to afford 523 mg (54%) of 3-iodo-1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazole as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 3.72 (s, 3H), 2.33 (t, J=6.4 Hz, 2H), 2.29 (s, 2H), 1.51 (t, J=6.4 Hz, 2H), 1.02 (s, 6H). Also isolated 160 mg (17%) of 3-iodo-2,6,6-trimethyl-4,5,6,7-tetrahydro-2H-indazole as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 3.87 (s, 3H), 2.41 (s, 2H), 2.36 (t, J=6.6 Hz, 2H), 1.54 (t, J=6.6 Hz, 2H), 1.00 (s, 6H).

Workup

stirringThe reaction mixture was stirred at 0° C. for 30 min
temperaturethen warmed to room temperature
stirringstirred for 1.5 h
customThe reaction was quenched with water
extractionextracted with EtOAc (2×)
dry with materialThe combined organics were dried over MgSO4
concentrationconcentrated
customThe residue was absorbed onto SiO2
custompurified by chromatography with 10% to 20% EtOAc/hexanes

Sources & evidence

ORD record: ord-93762a2410b248e6b066dbf350b5c23a
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

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