Trimethyl orthoformate → HCID 66937371, compound

HRID 408701Notes

Reaction equation

HRID 408701 reaction equation
[Cl:1][C:2]1[C:3]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][C:5]([N+:9]([O-])=O)=[C:6]([NH2:8])[CH:7]=1.[CH3:19]OC(OC)OC.S(S([O-])=O)([O-])=O.[Na+].[Na+].C(=O)(O)[O-].[Na+]>CN(C=O)C.C(O)(=O)C>[Cl:1][C:2]1[C:3]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][C:5]2[N:9]=[CH:19][NH:8][C:6]=2[CH:7]=1

Participants

7

Reactant 4

HCID 9005Trimethyl orthoformateHCID 24489Sodium Dithionite2×HCID 516892Sodium BicarbonateHCID 669372525-Chloro-2-nitro-4-phenoxyphenylamine

Product 1

HCID 66937371HCID 66937371, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-chloro-2-nitro-4-phenoxyphenylamine (0.810 g, 3.06 mmol) in DMF (12 mL) was added trimethylorthoformate (12 mL) followed by sodium dithionite (2.66 g, 15.3 mmol), and glacial acetic acid (1.5 mL). The reaction mixture was heated in a sealed tube at 100° C. for 14 h. Additional sodium dithionite (0.5 g) and acetic acid (1 mL) were added and heating was continued at 120° C. for an additional 3 h. The reaction flask was cooled in ice, added cautiously to half-saturated sodium bicarbonate solution (300 mL) and extracted with EtOAc. Combined organic layers were washed with 5% NaHCO3, brine, dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (hexanes:EtOAc, 0% to 5% over 20 minutes) to yield the titled compound as a yellow amorphous solid (0.57 g, 76%) as a mixture of tautomers. MS (ESI/CI): mass calcd. for C13H9ClN2O, 244; m/z found, 245 [M+H]+. 1H NMR (500 MHz, CDCl3): 9.55 (s, 1H), 8.06 (s, 1H), 8.0-7.2 (m, 2H), 7.32 (t, J=7.9 Hz, 2H), 7.09 (t, J=7.3 Hz, 1H), 6.96 (d, J=8.3 Hz, 2H).

Workup

  1. temperatureheating
  2. temperatureThe reaction flask was cooled in ice
  3. extractionextracted with EtOAc
  4. washCombined organic layers were washed with 5% NaHCO3, brine
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified (FCC) (hexanes:EtOAc, 0% to 5% over 20 minutes)

Sources & evidence

ORD record
ord-a392a6830fca4dcbbd3cd1011e7a2139
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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