Trifluoroacetic acid → HCID 69952803, compound

HRID 2268163Notes

Reaction equation

HRID 2268163 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=[O:4].[O:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[C:10]([CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27]C(C)(C)C)=[O:26])[CH2:21][CH2:20]2)=[N:9]1.[CH2:32](N(CC)CC)C.[CH2:39](Br)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(Cl)Cl>[C:3]([OH:5])(=[O:4])/[CH:2]=[CH:32]\[C:25]([OH:27])=[O:26].[C:40]1([CH2:39][N:22]2[CH2:23][CH2:24][CH:19]([CH2:18][CH2:17][C:10]3[C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[O:8][N:9]=3)[CH2:20][CH2:21]2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7498Benzyl BromideHCID 8471TriethylamineHCID 100195501-Piperidinecarboxylic acid, 4-[2-(1,2-benzisoxazol-3-yl)ethyl]-, 1,1-dimethylethyl ester

Product 1

HCID 69952803HCID 69952803, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoroacetic acid (TFA) (7 mL) was added dropwise to a cold (0° C.) solution of the piperidine formed in step d (0.50 g, 1.51 mmol) in methylene chloride (7 mL). The resulting solution was stirred at 0° C. for 30 min. Volatiles were removed under reduced pressure and excess TFA was removed by concentrating from toluene twice. The crude product was redissolved in methylene chloride (10 mL) and then triethylamine (0.42 mL, 3.01 mmol) and benzyl bromide (0.18 mL, 1.51 mmol) were added. The resulting mixture was stirred overnight (15 hours) at room temperature. The mixture was washed with water and brine and dried (MgSO4), filtered, and concentrated. Purification by silica gel flash chromatography (50% ethyl acetate/hexanes) gave the title compound (free base) (0.350 g, 73%) as a colorless oil.

Workup

  1. customVolatiles were removed under reduced pressure and excess TFA
  2. customwas removed
  3. concentrationby concentrating from toluene twice
  4. dissolutionThe crude product was redissolved in methylene chloride (10 mL)
  5. stirringThe resulting mixture was stirred overnight (15 hours) at room temperature
  6. washThe mixture was washed with water and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by silica gel flash chromatography (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0086f865c069466b87d99b71e56f727e
Source dataset
uspto-grants-2001_12
Patent number
US06326382B1

Reaction notes

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