Hydrochloric Acid → Atomoxetine impurity D CRS

HRID 2225045Notes

Reaction equation

HRID 2225045 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][CH:5]([OH:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Cl>>[CH3:1][NH:2][CH2:3][CH2:4][CH:5]([O:12][C:8]1[CH:9]=[CH:10][CH:11]=[C:6]([CH3:5])[CH:7]=1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 27339893-Methylamino-1-phenylpropanol

Product 1

HCID 11716259Atomoxetine impurity D CRS

Procedure

Under stirring, while maintaining the temperature between about 15° and about 25° C. with an ice-water bath, 8.55 g of 36% aqueous hydrogen chloride are dropped on the filtered organic phase, resulting in the crystallization and suspension of the 3-ATM Hydrochloride (mw 291.82). The suspension is stirred at about 20° C. for 1 hour, the solid is collected by filtration, washed twice with 35 ml of n-butyl acetate, and dried for 18 hours under vacuum at about 50° to about 60° C., yielding about 19.6 g of product, having a melting point of about 159° to about 160° C., and 1H-NMR data of 9.58 ppm, bs, 2H, 7.35-7.20 ppm, m, 5H, 7.01 ppm, t, 1H; 6.68-6.65 ppm, m, 2H, 6.59 ppm, dd, 1H, 5.30 ppm, dd, 1H; 3.10 ppm, quint, 2H; 2.57 ppm, t, 3H, 2.41 ppm, m, 2H, 2.22 ppm, s, 3H. The yield is 28 percent by weight based on the starting N-methyl-3-hydroxy-3-phenylpropylamine. The 3-ATM HCl is determined to be a mixture of enantiomers, with relative ratio: 99/1 by chiral HPLC.

Workup

  1. additiona mixture of enantiomers

Sources & evidence

ORD record
ord-272dc0263eb6471f91a328507b5d0372
Source dataset
uspto-grants-2008_05
Patent number
US07378553B2

Reaction notes

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