Triphenylphosphine → 5-Bromo-4-(cyclopropylmethoxy)-1-methyl-1H-indazole

HRID 1056984Notes

Reaction equation

HRID 1056984 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH3:11])[N:6]=[CH:5][C:4]=2[C:3]=1[OH:12].[CH:13]1([CH2:16]O)[CH2:15][CH2:14]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C(=O)(O)[O-].[Na+]>O1CCCC1>[Br:1][C:2]1[C:3]([O:12][CH2:16][CH:13]2[CH2:15][CH2:14]2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[N:6]=[CH:5]2

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 75644CyclopropanemethanolHCID 516892Sodium BicarbonateHCID 1369318035-Bromo-1-methyl-1H-indazol-4-ol

Product 1

HCID 1180939425-Bromo-4-(cyclopropylmethoxy)-1-methyl-1H-indazoleYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-bromo-1-methyl-1H-indazol-4-ol (73.7 mg, 0.324 mmol) and cyclopropyl carbinol (0.0386 mL, 0.489 mmol) in tetrahydrofuran (2.80 mL) was treated with triphenylphosphine (0.102 g, 0.390 mmol), cooled to 0° C., followed by dropwise addition of diisopropyl azodicarboxylate (0.0767 mL, 0.390 mmol). Reaction mixture was warmed to RT and stirred at RT for 16 h. The reaction mixture was poured into saturated sodium bicarbonate solution and extracted with ethyl acetate. Layers were separated and the organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give the crude product. Purification by flash column chromatography (100% hexanes to 100% CH2Cl2) gave the desired product (72 mg, 78%) as a yellow solid. LCMS calculated for C12H14BrN2O (M+H)+: m/z=281.0, 283.0. found: 281.0, 283.0.

Workup

  1. customReaction mixture
  2. temperaturewas warmed to RT
  3. extractionextracted with ethyl acetate
  4. customLayers were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude product
  10. customPurification by flash column chromatography (100% hexanes to 100% CH2Cl2)

Sources & evidence

ORD record
ord-6f06150813324ebab09149ab2f1e10d4
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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