Triphenylphosphine → 2-Amino-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanone

HRID 1685214Notes

Reaction equation

HRID 1685214 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:6]=1)=[O:4].[N-:16]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.C1COCC1>[NH2:16][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 521998p-Toluenesulfonic acid monohydrateHCID 27787872-Bromo-4'-fluoro-3'-(trifluoromethyl)acetophenone

Product 1

HCID 569716902-Amino-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanoneYield 150.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Cool a solution of 2-bromo-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanone (93% pure by HPLC, 1000 g; 3.51 mol) and THF (5 L) to <5° C. in an ice bath. Add a solution of sodium azide (239 g; 3.68 mol, 1.05 eq) in water (800 mL) drop wise over one hour at <5° C. After stirring at <5° C. for one hour, separate and discard the aqueous layer. While still cold, add the organic layer slowly over 3 hours to a solution of triphenylphosphine (920.2 g, 3.51 mol, 1.0 eq), p-toluenesulfonic acid monohydrate (1335 g, 7.02 mol, 2.0 eq), and THF (5 L). Maintain the temperature at <15° C. throughout this addition and solids precipitate during the addition. Stir the reaction mixture at <20° C. for 2 hours and then filter the solid, wash with THF (3×2 L), and dry at 50° C. under vacuum to give 1167.4 g (85%, 92% corrected for starting material purity) of 2-amino-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanone, 4-methylbenzenesulfonate as a white crystalline solid. HRMS (ESI) m/z (M+H) 222.0531 calculated for C9H8F4NO 222.0537

Workup

  1. customseparate
  2. temperatureMaintain the temperature at <15° C.
  3. additionthroughout this addition and solids
  4. customprecipitate during the addition
  5. stirringStir the reaction mixture at <20° C. for 2 hours
  6. filtrationfilter the solid
  7. washwash with THF (3×2 L)
  8. customdry at 50° C. under vacuum

Sources & evidence

ORD record
ord-c1de731336fa44d8ad91fdbd604683b1
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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