N,N-Dimethylaniline → (4-Phenoxyphenyl) 4-hydroxypiperidine-1-carboxylate

HRID 1721608Notes

Reaction equation

HRID 1721608 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)C1C=CC=CC=1.Cl[C:25](OC(Cl)(Cl)Cl)=[O:26].[OH:32][CH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.N1C=CC=CC=1>C1C=CC=CC=1.O1CCOCC1.C(Cl)Cl.C1COCC1>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([O:14][C:25]([N:36]2[CH2:37][CH2:38][CH:33]([OH:32])[CH2:34][CH2:35]2)=[O:26])=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 5

HCID 949N,N-DimethylanilineHCID 1049PyridineHCID 10426DiphosgeneHCID 132544-PhenoxyphenolHCID 79341Piperidin-4-ol

Product 1

HCID 2729092(4-Phenoxyphenyl) 4-hydroxypiperidine-1-carboxylateYield 185.1%

Reagents, catalysts & solvents 4

HCID 241BenzeneSolvent3×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-phenoxyphenol (30 g, 0.16 mol) and dimethylaniline (20.4 ml, 0.16 mol) in 200 ml of benzene plus 9 ml of dioxane was added dropwise over 15 minutes under a nitrogen atmosphere to a solution of trichloromethyl chloroformate (9.7 ml, 0.08 mol) in 60 ml of benzene at ice bath temperature. After the addition, the cooling bath was removed and the stirring continued for 24 hours. The reaction mixture was filtered and the filtrate was then added dropwise under a nitrogen atmosphere to a solution of 4-hydroxypiperidine (16.3 g, 0.16 mol) and pyridine (26.1 ml, 0.32 mol) in 150 ml each of benzene, methylene chloride and THF at ice bath temperature. After the addition, the reaction was stirred at ice bath temperature for 3 hours. The cooling bath was removed and the stirring continued overnight. The reaction mixture was diluted with benzene and washed with 1N HCl. The organic solution was separated, dried over anhydrous MgSO4 and the solvent removed under reduced pressure to give 46.4 g of a yellow mushy solid. Purification by HPLC (hexane:EtOAc) gave 13.3 g of a white solid. Recrystallization from diisopropyl ethermethanol gave the title compound as a white crystalline solid (10.4 g, 21%), mp 128°-130° C.

Workup

  1. additionAfter the addition
  2. customthe cooling bath was removed
  3. filtrationThe reaction mixture was filtered
  4. additionAfter the addition
  5. customThe cooling bath was removed
  6. customthe stirring continued overnight
  7. additionThe reaction mixture was diluted with benzene
  8. washwashed with 1N HCl
  9. customThe organic solution was separated
  10. dry with materialdried over anhydrous MgSO4
  11. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-7cf22972c8954ca2912777a8563c1892
Source dataset
uspto-grants-1996_04
Patent number
US05512565

Reaction notes

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