ITMI20070859A1 - PROCEDURE FOR THE PREPARATION OF REPLACED ARYLOSSIPROPYLAMINS - Google Patents

Description

Description of the patent for industrial invention entitled:

"PROCEDURE FOR THE PREPARATION OF SUBSTITUTED ARYLOXYPROPYLAMINS"

FIELD OF THE INVENTION

The present invention relates to a new process for the preparation of a compound of formula (I), or a salt thereof, either as a single isomer or as a mixture of isomers

where each of A and B, independently, is aryl or heteroaryl, optionally substituted and R is C1-C6alkyl. The compounds of formula (I) are particularly useful as antidepressants.

STATE OF THE TECHNIQUE

Compounds of formula (I), as defined herein, are for example the antidepressant "oxetines", inhibitors of the synaptic reabsorption of neuronal mediators, such as serotonin and noradrenaline. Examples of such "oxetines" are duloxetine, atomoxetine, fluoxetine and nisoxetine. Various synthesis methods are known for the preparation of these compounds. However, many of them make use of expensive and difficult to find starting products; and in any case their synthesis requires numerous steps, which make their preparation on an industrial scale expensive. Examples of such synthesis methods are those described in US 5,023,269; US 5,362,886 and EP 0457559 for duloxetine and US 4,018,895 for fluoxetine, atomoxetine or nisoxetine.

There is therefore a need for an alternative method of preparation of these compounds that uses starting products that are easy to find and prepare and also requires operating conditions that are well suited to industrial production, so as to reduce costs.

The method of the invention allows the obtaining of a compound of formula (I) as defined here, without the need to preventively protect the amino group and subsequently deprotect it. The production times and costs of this compound are therefore reduced.

DETAILED DESCRIPTION OF THE INVENTION

The subject of the invention is a process for the preparation of a compound of formula (I), or a salt thereof, both as a single isomer, and their mixtures

where each of A and B, independently, is an aryl or heteroaryl group, optionally substituted by 1 to 5 substituents, the same or different, selected from halogen, nitro, cyano, CrC6alkyl, optionally substituted by halogen, C1-C6alkylthio, C1-C6alkoxy, and -N (RaRb) where Raed Rb, equal or different, are C1-C6alkyl, or Raed Rb, taken with the nitrogen atom to which they are joined, form a pentatomic or hexatomic ring, saturated or unsaturated, optionally containing an additional 1 , 2 or 3 heteroatoms independently selected from nitrogen and oxygen; and R is C1-C6alkyl; comprising the reaction of a compound (II)

where A and B are as defined above, with a compound (III)

where R is as defined above; in the presence of one or more compounds of formula (IV)

where M is an alkaline or alkaline earth metal and E is a strong organic or inorganic base; if desired in the presence of a ligand; to obtain a compound of formula (V)

where R, A and B are as defined above, and its hydrolysis; and, if desired, the conversion of a compound of formula (I), or a salt thereof, into another compound of formula (I), or a salt thereof; and / or, if desired, the separation of a mixture of isomers of a compound of formula (I) into the individual isomers.

An isomer of a compound of formula (I) can be for example a geometric or optical isomer thereof, preferably it is an (R) or (S) enantiomer.

A salt of a compound of formula (I) is for example a salt with an acid or a base, preferably a pharmaceutically acceptable salt thereof as known, in particular the hydrochloride, hydrobromide, sulphate, mandelate, tartrate, dibenzoyl-tartrate, ditoluil- tartrate, oxalate, mesylate, maleate, preferably mandelate, hydrochloride and oxalate.

An A or B substituent, such as aryl, is for example phenyl or naphthyl. Preferably A is phenyl or 1-naphthyl, optionally substituted by C1-C4alkoxy or by C1-C4alkyl in turn optionally substituted by halogen. B as aryl is preferably phenyl.

A substituent A or B, such as heteroaryl, is for example a heterocyclic ring, typically monocyclic or bicyclic, unsaturated, optionally containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and sulfur. Examples of such heterocycle are thiophene, furan, pyrrole, pyridine, pyrazine, quinoline, indole, thionaphthene, benzofuran, quinoxaline and phthalazine. A preferred heteroaryl group B is thienyl.

A halogen atom is for example fluorine, chlorine, bromine or iodine; in particular fluorine or chlorine.

A C1-C6alkyl group is typically a C1-C4alkyl group, for example methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl or tert-butyl, in particular methyl, ethyl, propyl or isopropyl. When it is replaced by halogen, it can be replaced by 1 to 3 halogen atoms, as defined above; preferably it is trifluoromethyl.

A C1-C6alkylthio group is typically a C1-C4alkylthio group, in particular methylthio or ethylthio.

A C1-C6alkoxy group is typically a C1-C4alkoxy group, in particular methoxy, ethoxy or propoxy.

A -N group (RaRb) is for example a dimethylamino, methyl-ethylamino, diethylamino or diisopropylamino group. When a -N group (RaRb) forms a pentatomic or hexatomic ring, as defined above, it is for example a pyrrolidine, piperidino, piperazino, morpholino, pyrrole, imidazolyl or pyrazolyl radical.

In a compound of formula (IV) M as alkali or alkaline earth metal it is for example sodium, lithium, potassium or magnesium, preferably lithium; while E as a strong organic or inorganic base, as known, is for example a hydride, a C1-C6alkoxide, an alkyl carbanion, a silylanion, an amide anion. Examples of compounds of formula (IV) are butyl-lithium, hexyl-lithium, magnesium diisopropylamide, lithium diisopropylamide, lithium hexamethyldisilylazide, potassium tert-butylate, sodium or potassium hydride, preferably butyl-lithium and lithium diisopropylamide. When multiple compounds of formula (IV) are used, 2 or 3 are preferably used.

A ligand is typically a polyamine, for example a diamine chosen for example from N, N, N ', N'-tetramethylethylenediamine, N, N, N', N ", N" -pentamethyldiethylenetriamine, trans-N ^ N'N ' -tetramethylcyclohexantriamine, preferably Ν, Ν, Ν ', N' -tetramethylethylenediamine.

Preferred compounds of formula (I) are those where

A is a phenyl or naphthyl group, optionally substituted by C1-C4alkyl in turn optionally substituted by halogen; or from C1-C4alkoxy;

B is phenyl or thienyl;

R is C1-C4alkyl, in particular methyl; and their salts.

Specific examples of compounds of formula (I) are:

(+) - N-methyl-3- (1-naphthalenyloxy) -3- (2-thienyl) -propanamine (duloxetine); (-) - N-methyl-3- (2-methyl-phenyloxy) -3-phenyl-propanamine (atomoxetine); N-methyl- 3 - (4-trifluoromethyl-phenyloxy) - 3 - phenyl-propanamine (fluoxetine); N-methyl-3- (4-methoxy-phenyloxy) -3-phenyl-propanamine (nisoxetine); N-methyl-3- (1-naphthalenyloxy) -3- (2-thienyl) -propanamine;

N-methyl-3- (2-methyl-phenyloxy) -3-phenyl-propanamine;

and their salts.

The reaction between a compound of formula (II) and a compound of formula (III) can be carried out in the presence of a solvent, preferably an anhydrous organic solvent. Typically an aliphatic or aromatic hydrocarbon, for example hexane, toluene; petroleum ether; an ether, for example tetrahydro furan, dioxane, diethyl ether, methyl-tert-butyl ether; or a mixture of two or more, preferably two or three, of said solvents. Preferably the reaction is carried out in an ethereal solvent, in particular tetrahydrofuran or methyl-tert-butyl ether.

The stoichiometric ratio between a compound of formula (II) and the compound of formula (IV) is comprised between about 0.5 and 5, preferably between about 0.8 and 3. The reaction can be carried out at a temperature comprised between approximately - 80 ° C and 10 ° C and, preferably between about -15 ° C and 0 ° C.

The hydrolysis of a compound of formula (V) to give a compound of formula (I), or a salt thereof, can be carried out according to known methods, for example by using a mineral acid, such as sulfuric or hydrochloric acid, preferably acid sulfuric at a concentration of around 20%, in an organic solvent, for example an ether, typically tetrahydrofuran, dioxane, diethyl ether or methyl-tert-butyl ether, preferably methyl-tert-butyl ether; at a temperature between about 25 ° C and the reflux temperature of the reaction mixture, preferably around 50 ° C. A salt of a compound of formula (I), for example as hydrogen sulfate, can be converted into a compound of formula (I) by reaction with a basic agent, for example sodium hydroxide.

The conversion of a compound of formula (I) into another compound of formula (I), the separation of a mixture of isomers of a compound of formula (I) into the individual isomers, as well as the conversion of a compound of formula (I ) in its salt or vice versa can be carried out with known methods.

If desired, a compound of formula (I) can be resolved in its enantiomers according to known methods, such as described for atomoxetine in EP 0052492.

The compounds of formula (V) as defined above are new compounds and are a further subject of the invention.

Examples of such compounds are:

N-methyl-N- (3-phenyl-3- (2-methylphenyloxy) -propyl) sulphamic acid; N-methyl-N- (3- (2-thienyl) -3- (1-naphthalenyloxy) -propyl) sulphamic acid; N-methyl-N- (3-phenyl-3- (4-trifluoromethyl-phenyloxy) -propyl) sulphamic acid; And

N-methyl-N- (3-phenyl -3- (4-methoxy-phenyloxy) -propyl) sulphamic acid. A compound of formula (II), which may or may not be isolated, can be obtained by reaction between a compound of formula (VI), or a salt thereof, with a compound of formula (VII), where A, B are as defined first and X is a leaving group, for example a halogen atom, preferably chlorine or bromine, in particular bromine; or a hydroxyl group activated by esterification, for example through an alkanesulfonyloxy group, typically mesyloxy, or an arylsulfonyloxy group, typically tosyloxy, or a perfluoroalkanesulfonyloxy group, for example trifluoromethanesulfonayloxy and nonafluorobutanesulfonyloxy; preferably chlorine, bromine, iodine, mesyloxy, tosyloxy; more preferably chlorine.

The reaction, which can be summarized as follows

it is preferably carried out in the presence of a basic agent. Examples of such an agent are sodium, potassium, lithium or calcium hydroxide; sodium or potassium carbonate; a tertiary organic amine such as triethylamine or diisopropyl-ethylamine or an alkaline alkoxide such as sodium methylate or sodium ethylate. Preferably the basic agent is sodium or potassium hydroxide, or sodium or potassium carbonate.

The stoichiometric ratio between the compound of formula (VII) with the compound of formula (VI), or a salt thereof, is comprised approximately between 0.5 and 10, preferably between about 1 and 1.5.

The reaction can be carried out in the absence or in the presence of a solvent. Typically this solvent is an organic solvent such as a ketone, for example acetone, diethylketone, methyl-isobutylketone; or an ether, for example tetrahydrofuran, dioxane, diethyl ether; a chlorinated solvent, for example dichloromethane, dichloroethane, tetrachlorethylene, chlorobenzene or dichlorobenzene; an alkanol such as methanol, ethanol or isopropanol, or a mixture of two or more, in particular two or three, of said solvents with each other or with water. Preferably the reaction is carried out in a ketone solvent, in particular in acetone or a mixture thereof with water.

The reaction can be carried out at a temperature comprised between about 0 ° C and the reflux temperature of the reaction mixture, preferably between about 25 ° C and 50 ° C.

A compound of fomula (III), which may or may not be isolated, can be obtained by oxidation of a compound of formula (VIII)

where R is as defined above; if desired, in the presence of a catalyst and a basic agent.

The reaction, which can be summarized as follows

is carried out in the presence of an oxidizing agent, such as an inorganic oxidant, for example potassium permanganate, osmium tetroxide, sodium periodate or hydrogen peroxide, or an organic oxidant, typically a peracid, for example meta-chlorine perbenzoic acid or peracetic acid ; preferably it is sodium periodate.

A catalyst is typically a metal catalyst, for example a ruthenium (III) or ruthenium (IV) based catalyst, preferably ruthenium trichloride.

A basic agent is typically an inorganic base, for example potassium carbonate.

The reaction can be carried out in the absence or in the presence of a solvent, for example in an organic solvent such as a ketone, for example acetone, diethylketone, methyl-isobutylketone; or an ether, for example tetrahydrofuran, dioxane, diethyl ether; a chlorinated solvent, for example dichloromethane, dichloroethane, tetrachlorethylene, chlorobenzene or dichlorobenzene; an alkanol such as for example methanol, ethanol or isopropanol; an ester, for example methyl acetate, ethyl acetate, iso-propyl acetate; or a mixture of two or more, in particular two or three, of said solvents with each other or with water. Preferably the solvent is an ester, in particular ethyl acetate.

The reaction can be carried out at a temperature comprised between approximately -7 ° C and 25 ° C, preferably between -5 ° and 10 ° C.

The stoichiometric ratio between the compound of formula (VIII) and the oxidizing agent is approximately between 1 and 20, preferably between about 2 and 10.

The compounds of formula (III) where R is methyl or C3-C6alkyl are new compounds and constitute a further object of the invention.

An example of compounds of formula (III) is 3-methyl-1,2,3-oxatiazolidine 2,2-dioxide.

A compound of formula (VIII), which may or may not be isolated, can be prepared starting from a compound of formula (IX)

where R is as defined above, by means of a reaction, which can be schematized as follows

and conducted in the presence of donyl chloride and a base, typically an organic base, such as an amine, for example trimethylamine or triethylamine, preferably triethylamine.

The reaction can be carried out in a solvent, typically an organic solvent such as a chlorinated solvent, for example dichloromethane, dichloroethane, tetrachlorethylene, chlorobenzene, or dichlorobenzene; a hydrocarbon, e.g., hexane, heptane, or toluene; or a mixture of two or more, preferably two or three, of said solvents, with each other. Preferably the reaction is carried out in dichloromethane.

The stoichiometric ratio between the compound of formula (IX) and the donyl chloride is comprised approximately between 0.5 and 5, preferably between about 0.8 and 3.

The reaction can be carried out at a temperature comprised between approximately -20 ° C and the reflux temperature of the reaction mixture, preferably between -15 ° and 50 ° C.

The compounds of formula (VI), (VII) and (IX) are known or can be obtained with known methods.

The following examples illustrate the invention.

Example 1

N-methyl-3- (2-methylphenyloxy) -3-phenyl-propylamine (I)

A solution of N-methyl-N- (3-phenyl-3- (2-methylphenyloxy) -propyl) sulphamic acid (10 g; 0.03 mol) is charged into a three-neck reactor equipped with a mechanical stirrer and thermometer. methyl-tert-butyl ether.

Keeping the resulting solution under vigorous stirring, a solution (30 g) of sulfuric acid (20% w / w) is added and the biphasic mixture is heated at 50 ° C for 16 hours.

The mass is then allowed to cool to room temperature and the aqueous phase which contains the product in solution as a hydrogen sulfate salt is separated.

This solution is loaded into a reactor equipped with a mechanical stirrer and treated with a sodium hydroxide solution (50% w / w) up to a clearly basic pH.

The product is extracted with ethyl acetate, the organic phase is dried with anhydrous sodium sulphate and filtered. The filtered solution is reduced to residue by distillation of the solvent under reduced pressure.

The product is obtained with a yield of 66.7%.

Proceeding in the same way, the following compounds can be obtained: N-methyl-3- (1-naphthalenyloxy) -3- (2-thienyl) -propanamine;

N-methyl- 3 - (4-trifluoromethyl-phenyloxy) - 3 - phenyl-propanamine (fluoxetine); N-methyl-3- (4-methoxy-phenyloxy) -3-phenyl-propanamine (nisoxetine).

The N-methyl-3- (2-methylphenyloxy) -3-phenyl-propylamine and N-methyl-3- (1-naphthalenyloxy) -3- (2-thienyl) -propanamine compounds can be resolved into their respective enantiomers, according to with known methods, to obtain respectively:

(-) - N-methyl-3- (2-methyl-phenyloxy) -3-phenyl-propanamine (atomoxetine); and (+) - N-methyl-3- (1-naphthalenyloxy) -3- (2-thienyl) -propanamine (duloxetine).

Example 2

N-methyl-N- (3-phenyl-3- (2-methylphenyloxy) -propyl) sulphamic acid (V) In a three-neck reactor equipped with mechanical stirrer and thermometer, under nitrogen flow, o-tolyl- benzyl ether (21.5 g; 0.11 mol) and methyl-tert-butyl ether (20 ml) and cooled to a temperature of about -10 ° C.

While stirring and cooling to prevent the temperature from exceeding -8 ° C, add: a solution (140 ml) 1M of lithium diisopropylamide in methyl-tert-butyl ether, a solution (45.5 ml; 0.11 mol) 2 , 5 M of butyllithium in hexane and finally tetramethylethylenediamine (17.2 ml; 0.11 mol).

A solution of 3-methyl-1,2,3-oxathiazolidine 2,2-dioxide (30 g; 0.22 mol) in tetrahydrofuran (15 ml) is then added drop by drop, avoiding that the temperature does exceed -2 ° C.

At the end of the addition, the reaction is quenched with cold water (150 ml); after keeping the resulting mixture under vigorous stirring at room temperature for a few minutes, the phases are allowed to separate.

The aqueous phase is acidified with concentrated hydrochloric acid up to PH = 2 and the product is extracted with ethyl acetate (200 ml); the organic phase is added with anhydrous sodium sulphate, filtered and brought to residue.

10 g (0.03mol) of product are obtained.

1HNMR (300 MHz, CDC13) d (ppm): 7.22-7.39 (m, 5H); 7.12 (d, 1H); 6.92 (t, 1H); 6.80 (t, 1H); 6.59 (d, 1H); 5.38 (dd, 1H); 3.51-3.71 (mb, 2H); 3.02 (s, 3H); 2.35-2.42 (m, 2H); 2.31 (s, 3H).

Proceeding in a similar way, the following compounds can be obtained: N-methyl-N- (3- (2-thienyl) -3- (1-naphthalenyloxy) -propyl) sulfamic acid; N-methyl-N- (3-phenyl-3- (4-trifluoromethyl-phenyloxy) -propyl) sulphamic acid; N-methyl-N- (3-phenyl -3- (4-methoxy-phenyloxy) -propyl) sulphamic acid.

Example 3

O-tolyl-benzyl ether (II)

In a three-necked flask equipped with reflux, magnetic stirrer, thermometer, are loaded: o-cresol (100 g; 0.925 mol), potassium iodide (7.7 g; 0.046 mol) and acetone (650 ml) under nitrogen flow . Sodium carbonate (166 g; 1.20 mol) is added while stirring the suspension. The resulting mixture is then heated to reflux and at the same time benzyl chloride (127 g; 1.00 mol) is dropped in 30 minutes.

After 18 hours it is concentrated to residue under reduced pressure, then water (400 ml) and toluene (200 ml) are added. It is heated until the salts dissolve, the phases are separated and the organic phase is washed with water. The organic phase is dried over sodium sulphate and evaporated to a residue.

156.1 g of o-tolyl-benzyl ether are obtained as oil.

1HNMR (300 MHz, CDC13) d (ppm): 7.50-7.29 (m, 5H); 7.12-7.23 (m, 2H); 6.84-6.93 (m, 2H); 5.16 (s, 2H); 2.33 (s, 3H).

Example 4

3-methyl-1,2,3-oxathiazolidine 2,2-dioxide (III)

In a three-neck reactor equipped with mechanical stirrer and thermometer, the following are loaded under stirring and in the following order: water (825 ml), sodium periodate 2.66 mol), ruthenium trichloride (1.15 g; 0.005 mol) and potassium carbonate ( 0.77 g; 0.005 mol).

This solution is brought to a temperature of -5 ° C and a solution of 3-methyl-1,2,3-oxathiazolidine 2-oxide (54 g; 0.45 mol) in ethyl acetate is added drop by drop ( 500 ml), taking care that the temperature does not exceed 5 ° C.

It is left to react for about 30 minutes and then the organic phase is separated, which is washed with an aqueous solution (100 g) of sodium chloride (20% w / w).

The washing waters are removed, the organic phase is filtered, anhydrified with anhydrous sodium sulphate, filtered again and the product residues.

The product is obtained with a yield of 75%.

1HNMR (300 MHz, CDCl3) d (ppm): 4.55 (t, 2H); 3.54 (t, 2H); 2.83 (s, 3H).

Proceeding in the same way it is possible to obtain:

3-ethyl- 1,2,3-oxatiazolidine 2,2-dioxide.

Example 5

3-methyl-1,2,3-oxathiazolidine 2-oxide (VIII)

Donyl chloride (158.4 g; 1.33 mol) and dichloromethane (800 ml) are charged to room temperature in a three-neck reactor equipped with mechanical stirrer and thermometer, then it is cooled to about -15 ° C keeping the mixture under vigorous stirring and the system is conditioned in a nitrogen atmosphere.

A solution consisting of N-methylethanolamine (100 g; 1.33 mol), triethylamine (270 g; 2.66 mol) and dichloromethane (200 ml) is then dropped, taking care that the temperature remains between -5 and 0 ° C.

The mixture is left to react for two hours, causing the temperature to rise to 5 ° C, then the reaction is quenched with ice water (400 ml).

After waiting about 15 minutes, keeping the mixture under stirring, it is left to stand to allow the separation of the phases and the methylene phase is recovered, which is concentrated to about half its volume by distillation of dichloromethane.

The methylene phase is washed a second time with water (100 ml) and then the product is brought to residue.

110 g of product are obtained as oil (yield 68.3%).

1HNMR (300 MHz, CDCl3) d (ppm): 4.76 (ddd, 1H); 4.32 (ddd, 1H); 3.46 (ddd, 1H); 3.32 (ddd, 1H); 2.74 (s, 3H).

Example 6

N-methyl-3- (2-methylphenyloxy) -3-phenyl-propylamine hydrochloride (I) N-methyl-3- (2-methylphenyloxy) -3-phenylpropylamine (5 g; 0.02 mol) dissolves in a reactor in ethyl acetate (25 ml) and the solution is acidified with gaseous hydrochloric acid to pH = 4.

The hydrochloride salt precipitates as a white solid and is filtered, washed with ethyl acetate (10 ml) and dried in an oven at 50 ° C. 3.9 g of product are obtained.

<1> HNMR (300 MHz, CDCl3) d (ppm): 7.20-7.38 (m, 5H); 7.12 (d, 1H); 6.95 (t, 1H); 6.79 (t, 1H); 6.61 (d, 1H); 5.29 (dd, 1H); 2.79 (m, 2H); 2.41 (s, 3H); 2.26 (s, 3H); 2.12-2.24 (m, 1H); 1.98-2.09 (m, 1H).

Proceeding in the same way, the following compounds can be obtained: N-methyl-3- (1-naphthalenyloxy) -3- (2-thienyl) -propanamine hydrochloride;

N-methyl-3- (4-trifluoromethyl-phenyloxy) -3-phenyl-propanamine hydrochloride; N-methyl-3- (4-methoxy-phenyloxy) -3-phenyl-propanamine hydrochloride.

Claims (11)

CLAIMS 1. Process for the preparation of a compound of formula (I), or a salt thereof, either as a single isomer or mixtures thereof where each of A and B, independently, is an aryl or heteroaryl group, optionally substituted by 1 to 5 substituents, the same or different, selected from halogen, nitro, cyano, C1-C6alkyl optionally substituted by halogen, C1-C6alkylthio, C1- C6alkoxy, and -N (RaRb) where Raed Rb, equal or different, are C1-C6alkyl, or Raed Rb, taken with the nitrogen atom to which they are joined, form a pentatomic or hexatomic ring, saturated or unsaturated, optionally containing further 1, 2 or 3 heteroatoms independently selected from nitrogen and oxygen; and R is C1-C6alkyl; comprising the reaction of a compound (II) where A and B are as defined above, with a compound (III) where R is as defined above; in the presence of one or more compounds of formula (IV) where M is an alkaline or alkaline earth metal and E is a strong organic or inorganic base; if desired in the presence of a ligand; to obtain a compound of formula (V) where R, A and B are as defined above; and its hydrolysis; and, if desired, converting a compound of formula (I), or a salt thereof, into another compound of formula (I), or a salt thereof; and / or, if desired, the separation of a mixture of isomers of a compound of formula (I) into the individual isomers. 2. Process according to claim 1 wherein M as the alkali or alkaline earth metal is sodium, lithium, potassium or magnesium. 3. Process according to claim 1 wherein E as the strong organic or inorganic base is selected from a hydride, an alkoxide, an alkyl carbanion, a silylanion, and an amide anion. 4. Process according to claim 1 wherein the compound of formula (IV) is selected from butyl-lithium, hexyl-lithium, magnesium diisopropylamide, lithium diisopropylamide, lithium hexamethyldisilylazide, potassium tert-butylate and sodium or potassium hydride. 5. Process according to claim 1 wherein the ligand is a polyamine. 6. Process according to claim 1 wherein the reaction is carried out in an anhydrous organic solvent. 7. Process according to claim 1 wherein the stoichiometric ratio between a compound of formula (II) and the compound of formula (IV) is comprised between about 0.5 and 5. 8. A compound of formula (V) where A, B and R are as defined in claim 1. 9. A compound of formula (V), according to claim 8, which is N-methyl-N- (3-phenyl-3- (2-methylphenyloxy) -propyl) sulfamic acid; N-methyl-N- (3- (2-thienyl) -3- (1-naphthalenyloxy) -propyl) sulphamic acid; N-methyl-N- (3-phenyl-3- (4-trifluoromethyl-phenyloxy) -propyl) sulfamic acid; or N-methyl-N- (3-phenyl -3- (4-methoxy-phenyloxy) -propyl) sulphamic acid. 10. A compound of formula (III) where R is methyl or C3-C6alkyl. 11. A compound of formula (III) according to claim 10 which is 3-methyl-1,2,3-oxathiazolidine 2,2-dioxide.