Nitrogen → 4-[3-(4-Fluorophenoxy)phenyl]but-3-yn-2-ol

HRID 861684Notes

Reaction equation

HRID 861684 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9](I)[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:35][CH:36]([OH:39])[C:37]#[CH:38].C(NC(C)C)(C)C.N#N>[Cu]I.CC#N.CC#N.Cl[Pd]Cl.C(OC)(C)(C)C>[F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9]([C:38]#[C:37][CH:36]([OH:39])[CH3:35])[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 7912DiisopropylamineHCID 11776TriphenylphosphineHCID 162393-Butyn-2-olHCID 27373453-(4-Fluorophenoxy)iodobenzene

Product 1

HCID 197045224-[3-(4-Fluorophenoxy)phenyl]but-3-yn-2-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 15413tert-Butyl methyl etherSolvent

Procedure

A 30-gallon, glass-lined reactor was charged with 3-(4-fluoro-phenoxy)-iodobenzene (10.0 kg), copper(I) iodide (60.6 g), triphenyl-phosphine (95.0 g), bis(acetonitrile)palladium(II) chloride, and methyl t-butyl ether (27 kg). The mixture was cooled to 0°-10° C. and 55% aqueous 3-butyn-2-ol (4.20 kg) was added. Diisopropylamine (3.8 kg) was added to initiate the reaction and N2 was bubbled up from the bottom valve for a few minutes to agitate the reaction mixture. The reaction mixture was agitated at 15°-25° C. for 1.5 hours and then quenched by addition of 28% aqueous ammonia (12 kg) and brine (30 kg). The layers were separated and the organic phase was washed sequentially with brine (35 kg), 10% aqueous HCl (18 kg), 10% aqueous NaHCO3 (18 kg), and brine (35 kg). The organic phase was then stirred for 45 minutes with anhydrous MgSO4 (1.5 kg), PWA carbon (1.0 kg), and Ultra Norit C (1.0 kg) and filtered to give a solution of 4-[3-(4-fluorophenoxy)phenyl]-3-butyn-2-ol in methyl t-butyl ether which was used in the next step.

Workup

  1. temperatureThe mixture was cooled to 0°-10° C.
  2. customwas bubbled up from the bottom valve for a few minutes
  3. stirringThe reaction mixture was agitated at 15°-25° C. for 1.5 hours
  4. customquenched by addition of 28% aqueous ammonia (12 kg) and brine (30 kg)
  5. customThe layers were separated
  6. washthe organic phase was washed sequentially with brine (35 kg), 10% aqueous HCl (18 kg), 10% aqueous NaHCO3 (18 kg), and brine (35 kg)
  7. stirringThe organic phase was then stirred for 45 minutes with anhydrous MgSO4 (1.5 kg), PWA carbon (1.0 kg), and Ultra Norit C (1.0 kg)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-b476f5ec91444ec994fdf10d7c9edf05
Source dataset
uspto-grants-1998_02
Patent number
US05714633

Reaction notes

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