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1. (WO2007009405) A METHOD FOR THE PREPARATION OF (R)-N-METHYL-3-(2-METHYLPHENOXY)-3-PHENYLPROPYLAMINE HYDROCHLORIDE (ATOMOXETINE)
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/2007/009405 International Application No.: PCT/CZ2005/000091
Publication Date: 25.01.2007 International Filing Date: 01.12.2005
IPC:
C07C 213/06 (2006.01) ,C07C 215/30 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
213
Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
06
from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
215
Compounds containing amino and hydroxy groups bound to the same carbon skeleton
02
having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
22
the carbon skeleton being unsaturated
28
and containing six-membered aromatic rings
30
containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
Applicants:
ZENTIVA, A.S. [CZ/CZ]; U kabelovny 130 102 37 Praha 10, CZ (AllExceptUS)
RIDVAN, Ludek [CZ/CZ]; CZ (UsOnly)
HRUBY, Petr [CZ/CZ]; CZ (UsOnly)
RADL, Stanislav [CZ/CZ]; CZ (UsOnly)
ZATOPKOVA, Monika [CZ/CZ]; CZ (UsOnly)
PLACEK, Lukas [CZ/CZ]; CZ (UsOnly)
Inventors:
RIDVAN, Ludek; CZ
HRUBY, Petr; CZ
RADL, Stanislav; CZ
ZATOPKOVA, Monika; CZ
PLACEK, Lukas; CZ
Agent:
JIROTKOVA, Ivana ; ROTT, RUZICKA & GUTTMANN Patent, Trademark & Law Office Nad Stolou 12 170 00 Praha 7, CZ
Priority Data:
PV 2005-47321.07.2005CZ
Title (EN) A METHOD FOR THE PREPARATION OF (R)-N-METHYL-3-(2-METHYLPHENOXY)-3-PHENYLPROPYLAMINE HYDROCHLORIDE (ATOMOXETINE)
(FR) PROCEDE D'ELABORATION D'HYDROCHLORURE DE (R)-N-METHYL-3-(2-METHYLPHENOXY)-3-PHENYLPROPYLAMINE (ATOMOXETINE)
Abstract:
(EN) Racemic N-benzyl-N-methyl-3-(2-methylphenoxy)-3-phenylpro&rgr;ylamine (VIII) is an intermediate for obtaining atomoxetine. Racemic N-benzyl-N-methyl-3-(2-methylphenoxy)-3- phenylpropylamine (VIII) further reacts in a solution of an organic solvent with an optically active acid producing a mixture of diastereoisomers, which are subsequently resolved by crystallization and converted to the respective (R) and (S) enantiomers of N-benzyl-N-methyl- 3-(2-methylphenoxy)-3-phenylpropylamine by treatment with an organic or inorganic base. The (R)-enantiomer of N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine ((R)-VIII) is further subjected to debenzylation by means of an alkyl or aryl chloro formate yielding an alkyl/aryl (R)-3-(2-methylphenoxy)-3-phenylpropylmethylcarbamate ((R)-IX), which is then hydrolyzed in the basic environment yielding the base of (R)-N-methyl-3-(2-methylphenoxy)- 3-phenylpropaneamine, which is finally converted to (R)-N-methyl-3-(2-methylphenoxy)-3- phenylpropanamine hydrochloride ((R)-I) by treatment with hydrochloric acid.
(FR) La N-benzyl-N-méthyl-3-(2-méthylphénoxy)-3-phénylpro?ylamine (VIII) racémique est un intermédiaire permettant d'obtenir l'atomoxétine. En outre, en réagissant dans une solution d'un solvant organique avec un acide optiquement actif, elle produit un mélange de diastéréoisomères qui se résolvent ensuite par cristallisation, puis se convertissent en (R) et (S) énantiomères de la of N-benzyl-N-méthyl-3-(2-méthylphénoxy)-3-phénylpropylamine par traitement avec une base organique ou inorganique. Le (R)-énantiomère de la of N-benzyl-N-méthyl-3-(2-méthylphénoxy)-3-phénylpropylamine ((R)-VIII) est ensuite soumis à débenzylation par un chloro-formate d'alkyle ou aryle, ce qui donne un alkyle/aryle (R)-3-(2-méthylphénoxy)-3-phénylpropylméthylcarbamate ((R)-IX). Ce dernier est ensuite hydrolysé en environnement basique, ce qui donne la base de (R)-N-méthyl-3-(2-méthylphénoxy)-3-phénylpropaneamine qu'un traitement à l'acide chlorhydrique convertit finalement en hydrochlorure de (R)-N-méthyl-3-(2-méthylphénoxy)-3-phénylpropanamine ((R)-I).
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Designated States: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LT, LU, LV, MC, NL, PL, PT, RO, SE, SI, SK, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)