Trifluoroacetic acid → HCID 68433377, compound

HRID 1162846Notes

Reaction equation

HRID 1162846 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]([NH:25][C:26](=O)OC(C)(C)C)[CH2:11][N:12]([C:21](=[O:24])CBr)[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([O:8][CH2:9][CH:10]1[CH2:11][N:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[C:21](=[O:24])[CH2:26][NH:25]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68433262HCID 68433262, compound

Product 1

HCID 68433377HCID 68433377, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 2-(benzyloxy)-1-{[(bromoacetyl)(4-fluorobenzyl)amino]methyl}ethylcarbamate (2.79 g, 5.47 mmol) in CH2Cl2 (28 mL) was added trifluoroacetic acid (10 ml). The reaction was stirred at ambient temperature under inert atmosphere for 2 h and then concentrated in vacuo, azeotroping the residual oil with CHCl3. The resulting residue was dissolved in CH2Cl2 (100 mL) and treated with Hünig's base (10 mL). The solution was stirred at ambient temperature under inert atmosphere for 18 h. The solvent was removed in vacuo, and the remaining residue was partitioned between EtOAc and saturated aqueous NaHCO3 solution. The organic layer was washed with water and brine, dried over Na2SO4, and concentrated in vacuo. Purification by silica gel chromatography (EtOAc to 10% MeOH/EtOAc) afforded the title compound as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.37-7.22 (m, 7H), 7.04-6.98 (m, 2H), 4.64 (d, J=14.8 Hz, 1H), 4.49-4.44 (m, 3H), 3.63 (dd, J=17.6, 41.2 Hz, 2H), 3.47 (dd, J=4.0, 9.6 Hz, 1H), 3.40 (dd, J=6.4, 9.2 Hz, 1H), 3.22-3.16 (m, 1H), 3.10-3.06 (m, 2H), 1.71 (br s, 1H). ES MS (M+1)=329.3.

Workup

  1. concentrationconcentrated in vacuo
  2. customazeotroping the residual oil with CHCl3
  3. dissolutionThe resulting residue was dissolved in CH2Cl2 (100 mL)
  4. additiontreated with Hünig's base (10 mL)
  5. stirringThe solution was stirred at ambient temperature under inert atmosphere for 18 h
  6. customThe solvent was removed in vacuo
  7. customthe remaining residue was partitioned between EtOAc and saturated aqueous NaHCO3 solution
  8. washThe organic layer was washed with water and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customPurification by silica gel chromatography (EtOAc to 10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-d6e244ef1dc7445d977d79b5671321ae
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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