Sodium Bicarbonate → HCID 14500418, compound

HRID 1762912Notes

Reaction equation

HRID 1762912 reaction equation
Cl.[CH2:2]([O:4][C:5]1[CH:20]=[CH:19][CH:18]=[CH:17][C:6]=1[O:7][CH2:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)[OH:10])[CH3:3].C(=O)(O)[O-].[Na+]>CO.O.[Pt]=O>[CH2:2]([O:4][C:5]1[CH:20]=[CH:19][CH:18]=[CH:17][C:6]=1[O:7][CH2:8][CH:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][NH:12]1)[OH:10])[CH3:3]

Participants

6

Reactant 2

HCID 516892Sodium BicarbonateHCID 14500439HCID 14500439, compound

Product 1

HCID 14500418HCID 14500418, compoundYield 74.6%

Reagents, catalysts & solvents 3

HCID 82844Platinum oxide (PtO)CatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of α-[(2-ethoxyphenoxy)methyl]-2-pyridinemethanol hydrochloride (10.0 g., 0.034 mole) in 150 ml of methanol was hydrogenated at room temperature for 2 hr in the presence of 1.40 g of platinum oxide. Solvent was removed by rotary evaporator and NMR showed that the desired piperidine compound was obtained (9.35 g). This hydrochloride salt was dissolved in 150 ml of water and the solution was made alkaline (pH=8) with sodium bicarbonate. The free base was extracted from this aqueous solution with methylene chloride. Removal of methylene chloride gave 6.73 g of α-[(2-ethoxyphenoxy)methyl]-2-piperidinemethanol. The entire amount of the piperidine-methanol derivative (6.73 g) was dissolved in a mixture of 50 ml of acetic anhydride and 50 ml of pyridine and the mixture was heated at 90° C. for 4 hr. The reaction mixture was then stirred overnight at room temperature. Excess acetic acid anhydride and pyridine were removed in vacuo. The sample was then pumped under vacuum to remove final traces of pyridine and acetic anhydride. Formation of the diacetate derivative was confirmed by mass spectral analysis. The diacetate (9.82 g, 0.03 mole, as a viscous oil) was dissolved in 100 ml of tetrahydrofuran. To this solution was added slowly and under nitrogen with stirring, lithium aluminum hydride (3.06 g, 0.078 mole). Vigorous evolution of hydrogen occurred. The reaction mixture was stirred for 2.5 hr at room temperature and then slowly quenched with isopropanol followed by water. The reaction mixture was filtered and washed with methanol. The solvent was removed in vacuo, and the resulting oil was then partitioned between water and chloroform. The chloroform was removed in vacuo to give 5.42 g of light brown oil. The maleate salt was prepared by mixing equimolar methanol solutions of the free base and maleic acid. Addition of diethyl ether caused crystallization of a solid. The solid was triturated with isopropyl ether followed by ethyl acetate to give 2.24 g (16.1%) of a brown solid, m.p. 111.5°-115.0° C.

Workup

  1. customSolvent was removed by rotary evaporator and NMR
  2. customwas obtained (9.35 g)
  3. extractionThe free base was extracted from this aqueous solution with methylene chloride
  4. customRemoval of methylene chloride

Sources & evidence

ORD record
ord-74fa57df1045455c95ae7151ec587a4a
Source dataset
uspto-grants-1989_05
Patent number
US04835164

Reaction notes

Loading…