Trifluoroacetic acid → 4-[2-(4-Aminophenyl)ethoxy]phenyl methanesulfonate

HRID 1716179Notes

Reaction equation

HRID 1716179 reaction equation
FC(F)(F)C(O)=O.[CH3:8][S:9]([O:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([NH:28]C(OC(C)(C)C)=O)=[CH:24][CH:23]=2)=[CH:15][CH:14]=1)(=[O:11])=[O:10]>C1(C)C=CC=CC=1>[CH3:8][S:9]([O:12][C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([NH2:28])=[CH:26][CH:27]=2)=[CH:17][CH:18]=1)(=[O:11])=[O:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866202044-{2-[4-(Tert-butoxycarbonylamino)phenyl]ethoxy}phenyl methanesulfonate

Product 1

HCID 115657774-[2-(4-Aminophenyl)ethoxy]phenyl methanesulfonate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Trifluoroacetic acid (7.95 mL, 11.8 g, 102 mmol) was added over 5 minutes to a slurry of 4-{2-[4-(tert-butoxycarbonylamino)phenyl]ethoxy}phenyl methanesulfonate (17.6 g @ 95%, 40.8 mmol) in toluene (176 mL) at 20° C., and then heated to 60° C. to form a dark brown solution. A seed of pure product (0.05% by weight) was added and the reaction mixture heated at 60° C. for 17 hours during which period a dense solid crystallized. The reaction mixture was cooled to 20° C. and the solid isolated by filtration, washed by displacement with toluene (26 mL) and dried in a vacuum oven at 40° C. to yield the title compound as a dense, buff-coloured solid (16.1 g, 94%). HPLC (Rt 6.0 mins); m.p. 131-133° C.; 1H NMR (400 MHz, d6-DMSO) δ 7.35 (2H, d, J=8.4 Hz), 7.26 (2H, dt, J=10.8, 3.0 Hz), 7.13 (2H, d, 8.0 Hz), 7.05 (2H, dt, J=10.8, 3.0 Hz), 4.19 (2H, t, J=6.6 Hz), 3.31 (3H, s), 3.02 (2H, t, J=6.6 Hz), 2.9-4.7 (br); 13C NMR (100.6 MHz, d6-DMSO) δ 157.12, 142.46, 135.56, 133.65, 130.04, 123.31, 121.02, 115.45, 68.43, 36.92 and 34.14; MS (ES+) 308 (M+H+, 100%).

Workup

  1. customto form a dark brown solution
  2. additionA seed of pure product (0.05% by weight) was added
  3. temperaturethe reaction mixture heated at 60° C. for 17 hours during which period a dense solid
  4. customcrystallized
  5. temperatureThe reaction mixture was cooled to 20° C.
  6. customthe solid isolated by filtration
  7. washwashed by displacement with toluene (26 mL)
  8. customdried in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-bb83f8c535584cca9d5af625a4e6e295
Source dataset
uspto-grants-2010_09
Patent number
US07803586B2

Reaction notes

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