Aluminium lithium hydride → N-(1-benzyl-4-piperidinyl)-2-hydroxymethyl-3-fluoroaniline

HRID 1708317Notes

Reaction equation

HRID 1708317 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([NH:20][C:21]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:22]=2[C:23](O)=[O:24])[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>O1CCCC1>[CH2:7]([N:14]1[CH2:15][CH2:16][CH:17]([NH:20][C:21]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:22]=2[CH2:23][OH:24])[CH2:18][CH2:19]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 540167532-(1-Benzyl-4-piperidinylamino)-6-fluorobenzoic acid

Product 1

HCID 19031041N-(1-benzyl-4-piperidinyl)-2-hydroxymethyl-3-fluoroanilineYield 73.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of lithium aluminum hydride (0.9 g) in anhydrous tetrahydrofuran (160 ml) is added 2-(1-benzyl-4-piperidinylamino)-6-fluorobenzoic acid (8.0 g) and the mixture is refluxed for 1 hour. After cooling, the reaction solution is poured into ice-water and then extracted with dichloromethane. The solvent is concentrated and to the resulting residue is added diethyl ether/n-hexane. The precipitated crystal is collected by filtration to give N-(1-benzyl-4-piperidinyl)-2-hydroxymethyl-3-fluoroaniline (5.6 g) as light yellow powders, m.p.: 167°-170° C. Compounds of formula II are prepared as taught in European patent application EP 0 470514 A1, published Feb. 2, 1992. The carbostryril derivatives of formula II of the present invention can be prepared by various processes, for example, by the processes shown in the following reaction schemes. ##STR460## wherein R is the same RA as defined above or a group of the formula: ##STR461## wherein n and R3B are the same as defined above, and D is a group of the formula: --CH=CHR14' (R14' is a lower alkoxy, phenyl or a halogen atom), a group of the formula: ##STR462## (R9 and R10 are each a lower alkyl), or a group of the formula: --C=CH, and Y is hydrogen atom or a lower alkyl.

Workup

  1. temperaturethe mixture is refluxed for 1 hour
  2. temperatureAfter cooling
  3. extractionextracted with dichloromethane
  4. concentrationThe solvent is concentrated and to the resulting residue
  5. additionis added diethyl ether/n-hexane
  6. filtrationThe precipitated crystal is collected by filtration

Sources & evidence

ORD record
ord-9d36ea0912844b7092a246a7f6f43bb7
Source dataset
uspto-grants-1994_10
Patent number
US05356904

Reaction notes

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