Trifluoroacetic acid → 2-[4-(4-Fluoro-phenoxy)-phenyl]-ethyl-methyl amine

HRID 474732Notes

Reaction equation

HRID 474732 reaction equation
C(O[C:6](=O)[N:7]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[CH:13][CH:12]=1)C)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl.C([O-])(O)=O.[Na+]>[F:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][C:14]2[CH:15]=[CH:16][C:11]([CH2:10][CH2:9][NH:7][CH3:6])=[CH:12][CH:13]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67773542{2-[4-(4-Fluoro-phenoxy)-phenyl]-ethyl}-methyl-carbamic acid tert-butyl ester

Product 1

HCID 677746132-[4-(4-Fluoro-phenoxy)-phenyl]-ethyl-methyl amineYield 93%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

Entire reaction was performed under argon atmosphere using syringe septa technique. {2-[4-(4-fluoro-phenoxy)-phenyl]-ethyl}-methyl-carbamic acid tert-butyl ester (1.578 mmol, 1 eq) was dissolved in dichloromethane (6 ml) and stirred at 0° C. for 5 min. TFA (15.778 mmol, 10 eq) was added and stirring was continued for 50 hours. Reaction mixture was diluted with 50 ml NaHCO3 (sat.) and extraction with DCM (3×20 ml) followed. Organic layers were combined and evaporated. Crude product was put on a previously conditioned SCX column (5 g). Column was washed with MeOH (2×10 ml) and then with 2M NH3/MeOH to retrieve the product, {2-[4-(4-fluoro-phenoxy)-phenyl]ethyl}-methyl-amine (1.468 mmol, yield=93%, purity=94%). [M+H]+=246.22 1H NMR (300 MHz, CDCl3) δ/ppm 2.43 (s, 3H), 2.72-2.86 (m, 4H), 6.84-7.03 (m, 5H), 7.10-7.17 (m, 2H), 7.24 (s, 1H)

Workup

  1. customEntire reaction
  2. stirringstirring
  3. waitwas continued for 50 hours
  4. customReaction mixture
  5. customevaporated
  6. washColumn was washed with MeOH (2×10 ml)

Sources & evidence

ORD record
ord-dfa2ad952941432c8f1aaa031070de84
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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