p-Toluenesulfonic acid → 5-Nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1771403Notes

Reaction equation

HRID 1771403 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2)([O-:3])=[O:2].CC1C=CC(S(O)(=O)=O)=CC=1.[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1.[OH-].[Na+]>C(Cl)Cl>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH:25]1[CH2:26][CH2:27][CH2:28][CH2:29][O:24]1)[N:8]=[CH:7]2)([O-:3])=[O:2]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 14798Sodium HydroxideHCID 215015-Nitroindazole

Product 1

HCID 151476265-Nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 5-nitro-1H-indazole (24.4 g, 150 mmol) and p-TSA (2.58 g, 14.98 mmol) in DCM (1000 mL) was treated with 3,4-dihydro-2H-pyran (41.0 mL, 449 mmol) over 5 min to provide a solution that was stirred at RT for 6 hr. The resulting dark reaction mixture was added to 2 M NaOH (250 mL) and the organic layer was separated, dried and then concentrated in vacuo to afford a black oil. This material was purified by filtering through a plug of silica (˜700 g), loading and eluting with DCM (>12 L) to yield 5-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole as a pale yellow solid (34.02 g, 133 mmol, 89% yield); Rt 2.06 min, no ionisation observed; 1H NMR (400 MHz, CDCl3) δ: 1.70-1.78 (3H, over-lapping m), 2.14 (2H, m), 2.51 (1H, m), 3.76 (1H, ddd), 4.01 (1H, m), 5.77 (1H, dd), 7.69 (1H, d), 8.21 (1H, d), 8.27 (1H, dd), 8.71 (1H, dd).

Workup

  1. customto provide a solution that
  2. customThe resulting dark reaction mixture
  3. customthe organic layer was separated
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customto afford a black oil
  7. customThis material was purified
  8. filtrationby filtering through a plug of silica (˜700 g), loading
  9. washeluting with DCM (>12 L)

Sources & evidence

ORD record
ord-d246199944c6469a9c56db982c5f8bab
Source dataset
uspto-grants-2016_02
Patent number
US09249125B2

Reaction notes

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