Methanol → 1,1-Dimethylethyl 2,3-dihydro-2-methyl-5-nitro-3-oxo-1H-indazole-1-carboxylate

HRID 2375928Notes

Reaction equation

HRID 2375928 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([N+:17]([O-:19])=[O:18])=[CH:14][CH:15]=2)[C:10](=[O:20])[NH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:21]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CCOC(C)=O.C1COCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([N+:17]([O-:19])=[O:18])=[CH:14][CH:15]=2)[C:10](=[O:20])[N:9]1[CH3:21])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 887MethanolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 59854581HCID 59854581, compound

Product 1

HCID 692755581,1-Dimethylethyl 2,3-dihydro-2-methyl-5-nitro-3-oxo-1H-indazole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a pre-dried flask were added 5-nitro-3-oxo-2,3-dihydroindazole-1-carboxylic acid tert-butyl ester (0.65 g, 2.33 mmol), triphenylphosphine (0.92 g, 3.50 mmol), methanol (115 μL, 2.80 mmol) and anhydrous THF (10 mL). The flask was evacuated and purged with N2 then cooled to 0° C. and diisopropylazodicarboxylate (690 μL, 3.50 mmol) added dropwise over 5 min. The mixture was stirred at rt overnight then diluted with EtOAc and partitioned over water. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. Purification by column chromatography on silica gel (Jones, 50 g) loading and eluting in DCM revealed the title compound as a white powder. 1H NMR (400 MHz, CDCl3): δ=1.68 (s, 9H), 4.21 (s, 3H), 8.10 (d, J=8.8 Hz, 1H), 8.39 (dd, J=9.2 Hz, 2.4 Hz, 1H), 8.61 (d, J=2.0 Hz, 1H). MS (ES+): m/z 294.3 (20) [MH+]. The N-alkylation product methyl-5-nitro-3-oxo-2,3-dihydroindazole-1-carboxylic acid tert-butyl ester was also isolated. 1H NMR (400 MHz, CDCl3): δ=1.68 (s, 9H), 3.69 (s, 3H), 8.02 (d, J=9.2 Hz, 1H), 8.48 (dd, J=9.2, 2.4 Hz, 1H), 8.77 (d, J=2.0 Hz, 1H).

Workup

  1. customThe flask was evacuated
  2. custompurged with N2
  3. custompartitioned over water
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography on silica gel (Jones, 50 g) loading
  9. washeluting in DCM

Sources & evidence

ORD record
ord-01273cde179747b98184ee65c63c8f2a
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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