4'-Hydroxyacetophenone → 4-(4-Acetylphenoxy)piperidine-1-carboxylic acid tert-butyl ester

HRID 1593437Notes

Reaction equation

HRID 1593437 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34](O)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1>[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=2)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

6

Reactant 4

HCID 74694'-HydroxyacetophenoneHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 686059994-(4-Acetylphenoxy)piperidine-1-carboxylic acid tert-butyl esterYield 25.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of 1-(4-hydroxyphenyl)ethanone (1.48 g, 10.9 mmol) and tributylphosphine (3.0 g, 14.9 mmol) in toluene (20 ml) was treated dropwise at 0° C. with a solution of 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (2 g, 9.94 mmol) and 1,1′-(azodicarbonyl)dipiperidine (2.75 g, 10.9 mmol) in toluene (20 ml). The mixture was stirred at room temperature for 2 days then partitioned between aqueous sodium bicarbonate solution and dichloromethane. The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was chromatographed on silica gel eluting with a mixture of methanol/dichloromethane (1:9) to afford the title compound (0.81 g, 23%); MS(ES−) m/e 318 [M−H]−.

Workup

  1. customthen partitioned between aqueous sodium bicarbonate solution and dichloromethane
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe residue was chromatographed on silica gel eluting with a mixture of methanol/dichloromethane (1:9)

Sources & evidence

ORD record
ord-d1f43cbe2ba24e35a8e5253db4052da7
Source dataset
uspto-grants-2007_11
Patent number
US07297694B2

Reaction notes

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