Trifluoroacetic acid → [1-Acetyl-3-(4-methylbenzyl)piperidin-3-yl]methanol

HRID 1860643Notes

Reaction equation

HRID 1860643 reaction equation
F[C:2](F)(F)C(O)=O.[OH:8][CH2:9][C:10]1([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[CH2:15][CH2:14][CH2:13][N:12]([C:16](OC(C)(C)C)=[O:17])[CH2:11]1.C(N(CC)CC)C.CN(C1C=CC=CN=1)C.C(OC(=O)C)(=O)C>ClCCl>[C:16]([N:12]1[CH2:13][CH2:14][CH2:15][C:10]([CH2:9][OH:8])([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[CH2:11]1)(=[O:17])[CH3:2]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 18624164tert-Butyl 3-(hydroxymethyl)-3-(4-methylbenzyl)piperidine-1-carboxylate

Product 1

HCID 18624157[1-Acetyl-3-(4-methylbenzyl)piperidin-3-yl]methanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Trifluoroacetic acid (12.5 ml) was added to a solution of the product from STEP 3 (0.48 g, 1.4 mmol) in 12.5 ml dichloromethane at 0° C. The reaction was allowed to warm to room temperature. After 2 h, the reaction was concentrated, and dried in vacuo. The residue was dissolved in 20 ml dichloromethane, then triethylamine (1.82 g, 18.0 mmol) and dimethylaminopyridine (30 mg) were added. Acetic anhydride (1.13 ml, 12.0 mmol) was added to the above mixture at 0° C. The reaction mixture was allowed to warm to room temperature. After 18 h, the reaction was diluted with 150 ml dichloromethane, washed with 10 ml H2O, 5 ml brine, dried with MgSO4, and concentrated. The residue was dissolved in 25 ml methanol. An aqueous saturated K2CO3 solution (15 ml) was added at 0° C. The reaction was allowed to warm to room temperature. After 1.5 h, glacial acetic acid was added to adjust PH value to 6.5. The reaction was concentrated and product was extracted with ethyl acetate. The organic extracts were washed with brine, dried with MgSO4, and concentrated. The residue was purified by chromatography (SiO2, CH2Cl2/MeOH/NH4OH=90/10/0.2) to afford 0.14 g of an viscous oil. The 1H NMR spectrum of the product was consistent for the proposed structure.

Workup

  1. concentrationthe reaction was concentrated
  2. customdried in vacuo
  3. dissolutionThe residue was dissolved in 20 ml dichloromethane
  4. temperatureto warm to room temperature
  5. waitAfter 18 h
  6. washwashed with 10 ml H2O, 5 ml brine
  7. dry with materialdried with MgSO4
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in 25 ml methanol
  10. additionAn aqueous saturated K2CO3 solution (15 ml) was added at 0° C
  11. temperatureto warm to room temperature
  12. waitAfter 1.5 h
  13. additionglacial acetic acid was added
  14. concentrationThe reaction was concentrated
  15. extractionproduct was extracted with ethyl acetate
  16. washThe organic extracts were washed with brine
  17. dry with materialdried with MgSO4
  18. concentrationconcentrated
  19. customThe residue was purified by chromatography (SiO2, CH2Cl2/MeOH/NH4OH=90/10/0.2)

Sources & evidence

ORD record
ord-d1bef7076d5e4091a4a3733d23666fe5
Source dataset
uspto-grants-2003_03
Patent number
US06531494B1

Reaction notes

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