Hydrochloric Acid → HCID 178429017, compound

HRID 1892714Notes

Reaction equation

HRID 1892714 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][OH:9].Cl.[N:11]([O-])=O.[Na+].[CH3:15][C:16]1[CH:17]=[C:18]([OH:23])[CH:19]=[C:20]([CH3:22])[CH:21]=1.C([O-])([O-])=O.[Na+].[Na+]>O.CC#N>[OH:9][CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1/[N:1]=[N:11]/[C:21]1[C:20]([CH3:22])=[CH:19][C:18]([OH:23])=[CH:17][C:16]=1[CH3:15]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79483,5-DimethylphenolHCID 10340Sodium CarbonateHCID 214392-Aminobenzyl alcoholHCID 23668193Sodium Nitrite

Product 1

HCID 178429017HCID 178429017, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent

Conditions

Temperature
-5 °C

Procedure

(2-aminophenyl)methanol (4000 mg, 32.48 mmol) was dissolved in water (25 mL) with concentrated HCl (6 N, 7.00 mL, 42.2 mmol) and the solution was cooled in an ice/NaCl bath to −5° C., afterward sodium nitrite (2420 mg, 39 mmol) in 20 mL of water was added dropwise over 20 minutes. Solids precipitated out. The organic mixture/suspension was stirred at −5° C.→0° C. for 25 minutes. 5 mL CH3CN was added. The solution of 3,5-dimethylphenol (3970 mg, 32.5 mmol) in CH3CN (10 mL) was mixed with a solution of Na2CO3 (13.8 g, 130 mmol) in H2O (20 mL). The mixed solution was added to the above diazonium solution slowly at −5° C.→0° C. The mixture was stirred at −5° C.→0° C. for 2 hours. Brownish solids precipitated out. The mixture was neutralized with conc. HCl (12 N) and diluted with EtOAc. The suspension filtered through celite and washed with EtOAc which was used for extraction. After four extractions, the combine dark brownish organic layers were washed with brine, dried over Na2SO4 and concentrated, leading to dark brownish solids. The crude was dissolved in EtOAc and loaded to the column and purified by ISCO (120 g silica gel, EtOAc/Heptane: 0→45%), leading the desired product as orange solids. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.42 (s, 6H) 4.96 (d, J=5.66 Hz, 2H) 5.14-5.25 (m, 1H) 6.58 (s, 2H) 7.29-7.36 (m, 1H) 7.41-7.50 (m, 2H) 7.65 (d, J=0.78 Hz, 1H) 9.92 (s, 1H). LCMS: m/z=257.3 [M+H].

Workup

  1. customSolids precipitated out
  2. addition5 mL CH3CN was added
  3. stirringThe mixture was stirred at −5° C.→0° C. for 2 hours
  4. customBrownish solids precipitated out
  5. additiondiluted with EtOAc
  6. filtrationThe suspension filtered through celite
  7. washwashed with EtOAc which
  8. extractionwas used for extraction
  9. extractionAfter four extractions
  10. washthe combine dark brownish organic layers were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. dissolutionThe crude was dissolved in EtOAc
  14. custompurified by ISCO (120 g silica gel, EtOAc/Heptane: 0→45%)

Sources & evidence

ORD record
ord-a18d6c865597463aa8e3879846ebaedb
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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