Hydrochloric Acid → HCID 59354802, compound

HRID 655480Notes

Reaction equation

HRID 655480 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH3:14])([CH3:13])[C:10](=[O:15])[C:9]=2[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]3[CH:33]=[CH:32][C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[N:25]=3)=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.Cl.N([O-])=O.[Na+]>C(#N)C.O>[CH3:13][C:11]1([CH3:14])[C:10](=[O:15])[C:9]([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH2:23][C:24]3[CH:33]=[CH:32][C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[N:25]=3)=[CH:20][CH:21]=2)=[C:8]([C:5]2[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=2)[O:12]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 23668193Sodium NitriteHCID 59354866HCID 59354866, compound

Product 1

HCID 59354802HCID 59354802, compoundYield 23.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 5-(4-aminophenyl)-2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (80 mg, 0.18 mmol) in ACN: H2O (6 mL, 1:1) was added conc HCl (0.2 mL) at 0° C. under N2 atmosphere. The reaction mixture was stirred at 0° C. for 10 min. After being stirred for 5 min then added NaNO2 in water and stirred for 40 min at 0° C. The reaction mixture was stirred at 70° C. for 2 h. After completion of starting material (by TLC), reaction mass was diluted with water and extracted with EtOAc (2×25 mL). Combined organic layers were washed with water (2×5 mL), brine and dried over anhydrous Na2SO4. After filtration and evaporation, the crude material was purified by silica gel column chromatography to afford 2,2-dimethyl-5-phenyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (18 mg, 23%), as an off white solid. 1H NMR (400 MHz, CDCl3): δ 8.45 (d, J=8.5 Hz, 1H), 8.10 (d, J=7.9 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.75-7.62 (m, 3H), 7.52 (t, J=8.2 Hz, 1H), 7.45 (d, J=8.5 Hz, 1H), 7.32 (d, J=7.5 Hz, 2H), 7.21 (d, J=7.4 Hz, 2H), 7.03 (d, J=7.5 Hz, 2H), 5.42 (s, 2H), 1.51 (s, 6H). MS: [M+Na]: m/z=444.1, [M+H]: m/z=422.1. HPLC: 98.72% (RT-2.83 min), Column: Acquity BEH-C-18, 50×2.1 mm, 1.7 um. Mobile Phase: 0.025% TFA in Water (A), ACN (B), Flow rate: 0.5 ml/min (Gradient).

Workup

  1. stirringAfter being stirred for 5 min
  2. stirringThe reaction mixture was stirred at 70° C. for 2 h
  3. customAfter completion of starting material (by TLC), reaction mass
  4. extractionextracted with EtOAc (2×25 mL)
  5. washCombined organic layers were washed with water (2×5 mL), brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationAfter filtration and evaporation
  8. customthe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6a14f5a8c317409487c61d833ae0816f
Source dataset
uspto-grants-2011_12
Patent number
US08071595B2

Reaction notes

Loading…