Triethylamine → 4-{4-[(2-Tert-butylphenoxy)methyl]piperidin-1-yl}-2,2-dimethyl-4-oxobutanoic acid

HRID 2041991Notes

Reaction equation

HRID 2041991 reaction equation
Cl.[C:2]([C:6]1[CH:19]=[CH:18][CH:17]=[CH:16][C:7]=1[O:8][CH2:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)([CH3:5])([CH3:4])[CH3:3].C(N(CC)CC)C.[CH3:27][C:28]1([CH3:35])[CH2:32][C:31](=[O:33])[O:30][C:29]1=[O:34]>C1COCC1>[C:2]([C:6]1[CH:19]=[CH:18][CH:17]=[CH:16][C:7]=1[O:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:31](=[O:33])[CH2:32][C:28]([CH3:35])([CH3:27])[C:29]([OH:34])=[O:30])[CH2:12][CH2:11]1)([CH3:5])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 870672,2-Dimethylsuccinic anhydrideHCID 568310622-(tert-Butyl)phenyl 4-piperidinylmethyl ether hydrochloride

Product 1

HCID 595770434-{4-[(2-Tert-butylphenoxy)methyl]piperidin-1-yl}-2,2-dimethyl-4-oxobutanoic acidYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cold stirred solution of 4-[(2-tert-butylphenoxy)methyl]piperidine hydrochloride (0.20 g, 0.71 mmol) and triethylamine (0.10 g, 1.0 mmol) in THF (20.0 mL) was added 3,3-dimethyldihydrofuran-2,5-dione (0.11 g, 0.87 mmol) and the resulting mixture was warmed to room temperature. After 16 h the reaction mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and 1N hydrochloric acid and separated. The organic layer was washed with saturated sodium chloride, dried (MgSO4), filtered and concentrated under reduced pressure to give a white solid. The solid was recrystallized from hexane/ethyl acetate to provide 4-{4-[(2-tert-butylphenoxy)methyl]piperidin-1-yl}-2,2-dimethyl-4-oxobutanoic acid (0.19 g, 72%) as a white powder.

Workup

  1. concentrationAfter 16 h the reaction mixture was concentrated under reduced pressure
  2. customThe residue was partitioned between ethyl acetate and 1N hydrochloric acid
  3. customseparated
  4. washThe organic layer was washed with saturated sodium chloride
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give a white solid
  9. customThe solid was recrystallized from hexane/ethyl acetate

Sources & evidence

ORD record
ord-4218e09272894033935e4ca37431e70e
Source dataset
uspto-grants-2013_11
Patent number
US08586571B2

Reaction notes

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