2-Bromoanisole → 1-Boc-4-(2-methoxyphenyl)-4-hydroxypiperidine

HRID 276885Notes

Reaction equation

HRID 276885 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].CCCCCC.C([Li])CCC.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].[Cl-].[NH4+]>O1CCCC1>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31]([OH:34])([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[O:8][CH3:9])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

6

Reactant 4

HCID 113582-BromoanisoleHCID 25517Ammonium ChlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418244HCID 178418244, compound

Product 1

HCID 226295651-Boc-4-(2-methoxyphenyl)-4-hydroxypiperidineYield 62.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-Bromoanisole (5.0 g, 27 mmol) was dissolved in anhydrous tetrahydrofuran (60 ml) to which, while stirring, was subsequently added dropwise n-butyl lithium hexane solution (17 ml, 27 mmol) spending 20 minutes at −78° C. in an atmosphere of argon. After additional 30 minutes of stirring, to this was added dropwise anhydrous tetrahydrofuran solution (40 ml) of 1-t-butoxycarbonyl-4-piperidone (5.3 g, 27 mmol) spending 40 minutes. After additional 3.5 hours of stirring, to this was added saturated ammonium chloride aqueous solution (200 ml). The reaction product was extracted with ethyl acetate, washed with saturated brine and dried with anhydrous sodium sulfate. Then 5.2 g of the aforementioned compound of interest (17 mmol, 63% in yield) was obtained by evaporating the solvent under a reduced pressure.

Workup

  1. stirringAfter additional 30 minutes of stirring
  2. waitspending 40 minutes
  3. stirringAfter additional 3.5 hours of stirring
  4. extractionThe reaction product was extracted with ethyl acetate
  5. washwashed with saturated brine
  6. dry with materialdried with anhydrous sodium sulfate

Sources & evidence

ORD record
ord-bc63148425f84ac9ad0f273ede82b67e
Source dataset
uspto-grants-2002_03
Patent number
US06355642B1

Reaction notes

Loading…