Trifluoroacetic acid → 4-(1,2-Dihydro-5-acenaphthylenyl)piperidine

HRID 2056743Notes

Reaction equation

HRID 2056743 reaction equation
[CH2:1]1[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[C:6]([C:13]2(O)[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]2)=[CH:5][CH:4]=[C:3]3[CH2:2]1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.[OH-].[K+]>ClCCl.CO>[CH2:1]1[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[C:6]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=[C:3]3[CH2:2]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 12052TriethylsilaneHCID 14797Potassium HydroxideHCID 69307765HCID 69307765, compound

Product 1

HCID 693083194-(1,2-Dihydro-5-acenaphthylenyl)piperidine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of tert-butyl 4-(1,2-dihydro-5-acenaphthylenyl)-4-hydroxy-1-piperidinecarboxylate (0.44 g, 1.24 mmol) in dichloromethane (4 mL) was added triethylsilane (1.10 mL, 6.22 mmol) under nitrogen. The mixture was cooled to −30° C. then trifluoroacetic acid (0.48 mL, 6.22 mmol) added dropwise, maintaining the temperature below −25° C. After 2.5 h, the reaction mixture was allowed to warm to 0° C. and additional trifluoroacetic acid (0.48 mL, 6.22 mmol) added over 5 min. The reaction mixture was allowed to warm to room temperature and left to stir for 3 days. Ice was then added to the reaction mixture, followed by potassium hydroxide to a pH of 14, and the resultant slurry extracted with dichloromethane. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo to yield a yellow oil. The oil was dissolved in methanol and loaded onto an SCX-2 column. The column was washed with methanol, then a 2N solution of ammonia in methanol. Concentration in vacuo of the ammonia solution yielded 4-(1,2-dihydro-5-acenaphthylenyl)piperidine as a pale yellow oil.

Workup

  1. temperaturemaintaining the temperature below −25° C
  2. temperatureto warm to 0° C.
  3. temperatureto warm to room temperature
  4. waitleft
  5. additionIce was then added to the reaction mixture
  6. extractionthe resultant slurry extracted with dichloromethane
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto yield a yellow oil
  10. washThe column was washed with methanol
  11. concentrationConcentration in vacuo of the ammonia solution

Sources & evidence

ORD record
ord-8e5d0ee79af34648ae9dbcc0d84c9866
Source dataset
uspto-grants-2008_02
Patent number
US07335660B2

Reaction notes

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