2,6-Dimethylphenol → Methyl 4-{[4-(2,6-dimethylphenoxy)piperidin-1-yl]methyl}-3-isopropoxybenzoate

HRID 507989Notes

Reaction equation

HRID 507989 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=2[O:19][CH:20]([CH3:22])[CH3:21])[CH2:4][CH2:3]1.[CH3:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:25]=1O.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1.C(OCC)C>[CH3:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:25]=1[O:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=2[O:19][CH:20]([CH3:22])[CH3:21])[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 113352,6-Dimethylphenol2×HCID 13831Tributylphosphine2×HCID 730421,1'-(Azodicarbonyl)dipiperidine2×HCID 23157343Methyl 4-[(4-hydroxypiperidin-1-yl)methyl]-3-isopropoxybenzoate

Product 1

HCID 23157284Methyl 4-{[4-(2,6-dimethylphenoxy)piperidin-1-yl]methyl}-3-isopropoxybenzoateYield 36.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-[(4-hydroxypiperidin-1-yl)methyl]-3-isopropoxybenzoate (0.72 g, 2.34 mmol), 2,6-dimethylphenol (0.43 g, 3.51 mmol) and tributylphosphine (0.88 mL, 3.51 mmol) in anhydrous tetrahydrofuran (14 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.89 g, 3.51 mmol), and the mixture was stirred at room temperature for 12 hr. To the reaction mixture were added reagents (2,6-dimethylphenol, tributylphosphine and 1,1′-(azodicarbonyl)dipiperidine) in the same amount as mentioned above, and the mixture was further stirred for 12 hr. Diethyl ether (40 mL) was added to the reaction solution, the precipitate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1) to give the title compound (0.35 g, yield 36%) as a colorless oil.

Workup

  1. stirringwas further stirred for 12 hr
  2. filtrationthe precipitate was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-09029761993d4faa807ebcd5e9a8491f
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

Loading…