Methoxymethyl-triphenylphosphonium chloride → 5-(2-methoxy-vinyl)-7-methyl-1H-indazole

HRID 2099734Notes

Reaction equation

HRID 2099734 reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:24][C:25]([CH3:28])([O-])[CH3:26].[K+].C[C:31]1[CH:32]=CC=[C:35]2[C:39]=1[NH:38][N:37]=[C:36]2C=O>>[CH3:2][O:3][CH:4]=[CH:24][C:25]1[CH:28]=[C:35]2[C:39](=[C:31]([CH3:32])[CH:26]=1)[NH:38][N:37]=[CH:36]2

Participants

4

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 23665647Potassium tert-butoxideHCID 178423841HCID 178423841, compound

Product 1

HCID 690713565-(2-methoxy-vinyl)-7-methyl-1H-indazoleYield 94.3%

Procedure

Methoxymethyl triphenylphosphonium chloride (2.74 g, 8 mmol, 2.0 equiv.) and potassium tert-butoxide (1.35 g, 12 mmol, 3.0 equiv.) were weighed into a 250-mL oven-dried flask. Tetrahydrofuran (15 mL) was slowly introduced via syringe under nitrogen. After the resulting red solution was stirred at room temperature for 10 min, 7-methylindazole aldehyde (641 mg, 1.0 equiv.) was added in one portion. LCMS indicated that the reaction was complete within 1 h. The reaction was quenched with water and the mixture was then diluted with ethyl acetate. The layers were separated and the organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo to give a tan oil. The crude product was purified by flash column chromatography on silica gel (1:1 hexane/ethyl acetate) to afford the desired product as an off-white solid (710 mg, 94%). MS (ESI) [M+H]+=189; 1H NMR indicated a mixture of isomers (trans/cis ˜3:1). Trans isomer: 1H-NMR (400 MHz, CDCl3) δ 12.3 (br., 1H), 8.13 (s, 1H), 7.88 (s, 1H), 7.42 (s, 1H), 6.12 (d, J=7.0 Hz, 1H), 5.31 (d, J=7.0 Hz, 1H), 3.80 (s, 3H), 2.60 (s, 3H).

Workup

  1. customoven-dried flask
  2. additionTetrahydrofuran (15 mL) was slowly introduced via syringe under nitrogen
  3. waitwas complete within 1 h
  4. customThe reaction was quenched with water
  5. additionthe mixture was then diluted with ethyl acetate
  6. customThe layers were separated
  7. washthe organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customto give a tan oil
  11. customThe crude product was purified by flash column chromatography on silica gel (1:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a0f032e376114dbe8fcb62812293ba59
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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