Water → Tert-butyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-4-hydroxymethylpiperidine-1-carboxylate

HRID 394983Notes

Reaction equation

HRID 394983 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[CH2:18][CH2:19][CH2:20][C:21]1([C:34](OCC)=[O:35])[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1)=[CH:15][C:14]([O:39][CH3:40])=[CH:13][CH:12]=2.O.[OH-].[Na+]>O1CCCC1>[Cl:7][C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[CH2:18][CH2:19][CH2:20][C:21]1([CH2:34][OH:35])[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:32])([CH3:33])[CH3:31])=[O:28])[CH2:25][CH2:26]1)=[CH:15][C:14]([O:39][CH3:40])=[CH:13][CH:12]=2

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydride2×HCID 66688932Ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(tert-butyloxycarbonyl)piperidine-4-carboxylate

Product 1

HCID 22468565Tert-butyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-4-hydroxymethylpiperidine-1-carboxylateYield 96.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1.05 g of lithium aluminum hydride was added portionwise, with stirring and under an inert atmosphere, to a solution of 12.3 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(tert-butyloxycarbonyl)piperidine-4-carboxylate in 250 cm3 of tetrahydrofuran, at a temperature in the region of −20° C. After stirring for 2 hours at a temperature in the region of 20° C., 0.5 g of lithium aluminum hydride was added to the reaction mixture at a temperature in the region of −20° C. After 1 and a half hours, the reaction mixture was cooled to 0° C. and was then hydrolyzed by successive addition of 1.8 cm3 of water, 1.3 cm3 of 5N sodium hydroxide and 5.7 cm3 of water. After stirring for 30 minutes at a temperature in the region of 20° C., the reaction mixture was filtered and then washed with 400 cm3 of ethyl acetate. The filtrate was washed with 200 cm3 of saturated sodium chloride solution, dried over magnesium sulfate and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 10.9 g of tert-butyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-4-hydroxymethylpiperidine-1-carboxylate were obtained.

Workup

  1. additionwas added to the reaction mixture at a temperature in the region of −20° C
  2. filtrationthe reaction mixture was filtered
  3. washwashed with 400 cm3 of ethyl acetate
  4. washThe filtrate was washed with 200 cm3 of saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-0480aee5400643df90e308e50a6a38a8
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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