Triphenylphosphine → p-Toluenesulfonic acid

HRID 419746Notes

Reaction equation

HRID 419746 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)=[O:4].[N-:15]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.[C:39]1([CH3:49])[CH:44]=[CH:43][C:42]([S:45]([OH:48])(=[O:47])=[O:46])=[CH:41][CH:40]=1>C1COCC1.O>[NH2:15][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)=[O:4].[CH3:49][C:39]1[CH:44]=[CH:43][C:42]([S:45]([OH:48])(=[O:47])=[O:46])=[CH:41][CH:40]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 521998p-Toluenesulfonic acid monohydrateHCID 27783862-Bromo-1-[3-(trifluoromethyl)phenyl]ethan-1-one

Product 2

HCID 6101p-Toluenesulfonic acidHCID 133658842-Amino-1-[3-(trifluoromethyl)phenyl]ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

Charge 2-bromo-1-[3(trifluoromethyl)phenyl]-1-ethanone (1664.7 g; 1.00 equiv; 6.23 moles) and tetrahydrofuran (7500 mL) to a 12 L 3-necked round bottom flask (fitted with water-cooled condenser, nitrogen blanket, mechanical stirrer and cooling bath. Charge sodium azide (425.6 g; 1.05 equiv; 6.55 moles) in one portion. Rinse into the flask with water (135 mL). Stir the pale yellow slurry at RT under nitrogen. After 6 hours, add water (260 mL) and continue to stir overnight. Filter the resulting orange slurry over a thin pad of Celite® and rinse with THF (1 L). Divide the resulting solution into two equal portions (5146.5 g each). Charge two identical 22 L 3-necked round bottom flask (fitted with addition funnel, water-cooled condenser, nitrogen blanket, mechanical stirrer and cooling bath) with triphenylphosphine (889 g, 3.43 mol, 1.1 eq), p-toluenesulfonic acid monohydrate (1304 g, 6.86 mol, 2.2 eq) and THF (5.6 L). Add the two portions of intermediate mixture via addition funnels to the individual flasks over four hours, controlling the foaming from nitrogen evolution by addition rate and the temperature by use of an ice bath. On completion of addition stir the slurry at ambient temperature for two hours, then filter solids from both reactors onto the same filter. Wash both flasks and the combined cake with a total THF (4 L). Dry in a vacuum oven at 40° C. overnight to afford (2-Amino-1-(3-trifluoromethyl-phenyl)-ethanone)-, p-toluene sulfonate (1:1) as a white, crystalline solid (2340 g, 6.23 mol, 72%).

Workup

  1. temperaturecooled condenser
  2. temperaturenitrogen blanket, mechanical stirrer and cooling bath
  3. washRinse into the flask with water (135 mL)
  4. additionadd water (260 mL)
  5. stirringto stir overnight
  6. filtrationFilter the resulting orange slurry over a thin pad of Celite®
  7. washrinse with THF (1 L)
  8. additionCharge
  9. additionAdd the two portions of intermediate mixture
  10. additionvia addition funnels to the individual flasks over four hours
  11. additionby addition rate
  12. additionOn completion of addition
  13. stirringstir the slurry at ambient temperature for two hours
  14. filtrationfilter solids from both reactors onto the same filter
  15. washWash both flasks
  16. customDry in a vacuum oven at 40° C. overnight

Sources & evidence

ORD record
ord-e90d848143ac45e6a5c90f90aa96f6d6
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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