Water → 1-Benzyl-4-(pyridin-3-YL)piperidin-4-OL

HRID 1858824Notes

Reaction equation

HRID 1858824 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH2:13]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>COC(C)(C)C>[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]([OH:26])([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:22][CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 122863-BromopyridineHCID 192201-Benzyl-4-piperidoneHCID 178418339Butyllithium

Product 1

HCID 10940791-Benzyl-4-(pyridin-3-YL)piperidin-4-OLYield 60%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent2×

Conditions

Temperature
-75 °C

Procedure

(α) A solution of 16.7 g (106 mmol) of 3-bromo-pyridine in 200 ml of tert-butyl methyl ether was cooled to -75° C. Thereto there was added dropwise within 45 minutes a solution of 66 ml (106 mmol) of n-butyllithium (1.6M in hexane) and the mixture was stirred at -75° C. for one hour. Subsequently, a solution of 10.0 g (52.8 mmol) of 1-benzyl-4-piperidone in 50 ml of tert-butyl methyl ether was added dropwise at -70° C. to -75° C. and thereafter the mixture was stirred for 2 hours. Subsequently, the mixture was left to warm to room temperature. Thereafter, it was hydrolyzed with 50 ml of water and extracted with 100 ml of ethyl acetate. The organic phase was dried over magnesium sulphate and finally the solvent was evaporated under reduced pressure, with the product beginning to separate. From the evaporated mother liquor there were isolated by crystallization from a mixture of ethyl acetate and hexane a further 1.9 g, so that a total of 8.4 g (60% of theory) of 1'-benzyl-2',3',5',6'-tetrahydro-1'H-[3,4']bipyridinyl-4'-ol were obtained as a colourless solid; MS: 268 (M+H)+.

Workup

  1. stirringthe mixture was stirred for 2 hours
  2. waitSubsequently, the mixture was left
  3. temperatureto warm to room temperature
  4. extractionextracted with 100 ml of ethyl acetate
  5. dry with materialThe organic phase was dried over magnesium sulphate
  6. customfinally the solvent was evaporated under reduced pressure, with the product
  7. customto separate
  8. customFrom the evaporated mother liquor there were isolated by crystallization from a mixture of ethyl acetate and hexane a further 1.9 g

Sources & evidence

ORD record
ord-9a7c49e492aa428cb136545dd0c91083
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

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