Hydrochloric Acid → HCID 72700318, compound

HRID 716816Notes

Reaction equation

HRID 716816 reaction equation
[C:1]12([C:12]3[C:7](=[CH:8][CH:9]=[C:10]([OH:13])[CH:11]=3)[CH2:6][O:5]1)[CH2:4][CH2:3][CH2:2]2.C(#N)C.Cl[C:18]1[N:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][N:19]=1.Cl>C(OCC)(=O)C.[Fe]>[C:1]12([C:12]3[CH:11]=[C:10]([O:13][C:18]4[N:23]=[CH:22][C:21]([NH2:24])=[CH:20][N:19]=4)[CH:9]=[CH:8][C:7]=3[CH2:6][O:5]1)[CH2:4][CH2:3][CH2:2]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 825442-Chloro-5-nitropyrimidineHCID 71491180HCID 71491180, compound2×

Product 1

HCID 72700318HCID 72700318, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of spiro[1H-isobenzofuran-3,1′-cyclobutane]-5-ol (Intermediate 24, 50 mg, 0.28 mmol) in dry acetonitrile (4 mL) dipotassium carbonate (58.8 mg, 0.43 mmol) and then 2-chloro-5-nitro-pyrimidine (43.0 mg, 0.27 mmol) were added and the reaction mixture was stirred for 4 hours at room temperature. The reaction was diluted with ethyl acetate (20 ml) and washed with an aqueous saturated solution of ammonium chloride (2×10 ml). The organic layer was dried (Na2SO4), filtered and evaporated. The residue was dissolved in ethanol (5 mL)/water (1 mL). Iron (95.0 mg, 1.7 mmol) and an aqueous 6M solution of hydrogen chloride (0.05 ml, 0.3 mmol) were added and the reaction mixture was stirred at 50° C. for 3 hours. The catalyst was filtered off and the solution was diluted with an aqueous saturated solution of NaHCO3 (10 ml) and extracted with ethyl acetate (2×15 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 10 g as column and cyclohexane/ethyl acetate from 60:40 to 0:100 as eluent affording the title compound (24 mg) as a light yellow solid.

Workup

  1. washwashed with an aqueous saturated solution of ammonium chloride (2×10 ml)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. dissolutionThe residue was dissolved in ethanol (5 mL)/water (1 mL)
  6. stirringthe reaction mixture was stirred at 50° C. for 3 hours
  7. filtrationThe catalyst was filtered off
  8. additionthe solution was diluted with an aqueous saturated solution of NaHCO3 (10 ml)
  9. extractionextracted with ethyl acetate (2×15 ml)
  10. dry with materialThe organic layer was dried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated
  13. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 10 g as column and cyclohexane/ethyl acetate from 60:40 to 0:100 as eluent

Sources & evidence

ORD record
ord-a908009f4217425c8c6d6d26fc1b6f92
Source dataset
uspto-grants-2015_11
Patent number
US09193704B2

Reaction notes

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