p-Toluenesulfonic acid → HCID 86757942, compound

HRID 844475Notes

Reaction equation

HRID 844475 reaction equation
C1(C)C=CC(S(O)(=O)=[O:8])=CC=1.[Br:12][C:13]1[CH:18]=[CH:17][C:16](O)=[C:15]([F:20])[CH:14]=1.[O:21]1[CH:26]=[CH:25][CH2:24][CH2:23][CH2:22]1>C(Cl)Cl.CCCCCC>[Br:12][C:13]1[CH:18]=[CH:17][C:16]([C:26]2([OH:8])[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)=[C:15]([F:20])[CH:14]=1.[CH3:23][CH2:22][O:21][CH2:26][CH3:25]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 27249814-Bromo-2-fluorophenol

Product 1

HCID 86757942HCID 86757942, compound

Reagents, catalysts & solvents 1

HCID 21226440Methylenechloride HexaneSolvent

Procedure

p-Toluene sulfonic acid (0.40 g) was added to an ice-cooled solution of 4-Bromo-2-fluoro phenol (205.38, 1.075 mol) in dihydro-2H-pyran (452.23 g, 5.376 moles). The ice bath was removed after 30 min. and the mixture was stirred for two hours and then diluted with methylene chloride (500 ml). The methylene chloride solution was extracted with 10% aqueous KOH solution (3×500 ml), rinsed with water (3×500 ml), dried over MgSO4, filtered and rotavaped. The crude product was further dried overnight over a vacuum pump and then vacuum distilled. The first distillation fraction was unreacted phenol, (52.0 g) followed by a fraction of the protected phenol (212.29 g, 71.8%). The purified product was frozen in dry ice/acetone bath and then allowed to sit in the refrigerator over 2-3 days to obtain the Monomer IA2 intermediate as clear needle shaped crystals, mp=25-27° C., mp of the Monomer IA1 intermediate=62-63° C., TLC (1:1 CH2Cl2/hexane), Rf=0.42.

Workup

  1. customThe ice bath was removed after 30 min.
  2. additiondiluted with methylene chloride (500 ml)
  3. extractionThe methylene chloride solution was extracted with 10% aqueous KOH solution (3×500 ml)
  4. washrinsed with water (3×500 ml)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. dry with materialThe crude product was further dried overnight over a vacuum pump
  8. distillationvacuum distilled
  9. temperatureThe purified product was frozen in dry ice/acetone bath
  10. waitto sit in the refrigerator over 2-3 days
  11. customto obtain the Monomer IA2 intermediate as clear needle

Sources & evidence

ORD record
ord-22df4dc22e1e4156999fcdc435fe4148
Source dataset
uspto-grants-2002_04
Patent number
US06380340B1

Reaction notes

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