Chlorotrimethylsilane → HCID 56737061, compound

HRID 889428Notes

Reaction equation

HRID 889428 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH2:4].[CH:12]([NH:14][NH:15][CH:16]=O)=O.[Si](Cl)(C)(C)C.CCN(CC)CC>N1C=CC=CC=1>[F:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[N:4]1[CH:16]=[N:15][N:14]=[CH:12]1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 123421,2-HydrazinedicarboxaldehydeHCID 677852-Fluoro-5-nitroaniline

Product 1

HCID 56737061HCID 56737061, compoundYield 37.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-fluoro-5-nitroaniline (415 mg, 2.7 mmol) in pyridine (15 mL) was treated with N′-formylformohydrazide (703 mg, 7.98 mmol), and TMS-Cl (5.10 mL, 39.9 mmol) was then added dropwise. After the addition, Et3N (2.60 mL, 18.6 mmol) was added, and the reaction mixture was heated to 100° C. for 4 hours. The reaction mixture was then cooled to room temperature and concentrated to dryness. The resulting solid was suspended in H2O (25 mL) and filtered. The filtrate was extracted with EtOAc (4×20 mL), and the organics were dried (Na2SO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM and purified by flash chromatography (SiO2, hexanes to 100% EtOAc, 40 g column, 40 min. gradient) to afford Intermediate 28A (210 mg, 37.9%). HPLC: Rt=1.497 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). MS (ES): m/z=209.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (1H, s), 9.05 (1H, s), 8.72 (1H, dd, J=6.55, 2.77 Hz), 8.39-8.45 (1H, m), 7.85 (1H, t, J=9.57 Hz).

Workup

  1. additionwas then added dropwise
  2. additionwas added
  3. temperatureThe reaction mixture was then cooled to room temperature
  4. concentrationconcentrated to dryness
  5. filtrationfiltered
  6. extractionThe filtrate was extracted with EtOAc (4×20 mL)
  7. dry with materialthe organics were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe crude product was dissolved in a small amount of DCM
  11. custompurified by flash chromatography (SiO2, hexanes to 100% EtOAc, 40 g column, 40 min. gradient)

Sources & evidence

ORD record
ord-0867ec42c9ad41138bdb85ee9f9363d8
Source dataset
uspto-grants-2012_08
Patent number
US08252795B2

Reaction notes

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