Trifluoroacetic acid → 145815-98-1

HRID 2268173Notes

Reaction equation

HRID 2268173 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=[O:4].[O:8]1[C:12]2[CH:13]=[C:14]3[NH:19][C:18](=[O:20])[CH2:17][C:15]3=[CH:16][C:11]=2[C:10]([CH2:21][CH2:22][CH:23]2[CH2:28][CH2:27][N:26](C([O:31][C:32]([CH3:35])(C)C)=O)[CH2:25][CH2:24]2)=[N:9]1.C(=O)([O-])[O-:37].[Na+].[Na+].[CH2:42](Br)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C(Cl)Cl>[C:3]([OH:5])(=[O:4])/[CH:2]=[CH:35]\[C:32]([OH:37])=[O:31].[C:43]1([CH2:42][N:26]2[CH2:27][CH2:28][CH:23]([CH2:22][CH2:21][C:10]3[C:11]4[CH:16]=[C:15]5[CH2:17][C:18](=[O:20])[NH:19][C:14]5=[CH:13][C:12]=4[O:8][N:9]=3)[CH2:24][CH2:25]2)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7498Benzyl BromideHCID 10340Sodium CarbonateHCID 135525307HCID 135525307, compound

Product 1

HCID 135462830145815-98-1Yield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (TFA) (3.3 mL) was added dropwise to a cold (0° C.) solution of the piperidine formed in step e (0.50 g, 1.30 mmol) in CH2Cl2 (13 mL). After 30 min, the mixture was concentrated and excess TFA was removed by concentrating from toluene (2 to 3 times). The crude residue was dissolved in DMF (12.5 mL) and sodium carbonate (Na2CO3) (0.689 g, 6.50 mmol) and benzyl bromide (0.186 mL, 1.56 mmol) were added. The resulting mixture was stirred at room temperature for 4 hours. The reaction was filtered and the filtrate was concentrated in vacuo. The residue was dissolved in methylene chloride and washed with brine, and dried (MGSO4), filtered, and concentrated. Purification by silica gel chromatography (CH2Cl2→10% methanol/CH2Cl2) gave the title compound (free base) (0.343 g, 70%) as a white solid.

Workup

  1. concentrationthe mixture was concentrated
  2. customexcess TFA was removed
  3. concentrationby concentrating from toluene (2 to 3 times)
  4. dissolutionThe crude residue was dissolved in DMF (12.5 mL)
  5. filtrationThe reaction was filtered
  6. concentrationthe filtrate was concentrated in vacuo
  7. dissolutionThe residue was dissolved in methylene chloride
  8. washwashed with brine
  9. customdried (MGSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by silica gel chromatography (CH2Cl2→10% methanol/CH2Cl2)

Sources & evidence

ORD record
ord-fab4a8aea0584ea4b590f6af7b1a6ff2
Source dataset
uspto-grants-2001_12
Patent number
US06326382B1

Reaction notes

Loading…