Process for preparing substituted 2-alkoxycarbonyl-3-aminothiophenes
View Patent ↗The present invention relates to a process for preparing 4 -alkoxycarbonyl- 3 -aminothiophenes of the general formula (I) and/or their hydrochlorides of the formula (I)′ in which R 1 and R 2 are each as defined in the description, and/or their mono- or bisacetylated or mono- or bisformylated form, by reacting enamines of the formula (II) in which R 1 and R 2 are each as defined in the description, and/or their mono- or bisacetylated or mono- or bisformylated form, with a chlorinating agent in the presence of one or more diluents, and also to a process for preparing the compounds of the formula (II).
1. A process for preparing a 4-alkoxycarbonyl-3-aminothiophene of formula (I)
and/or a hydrochloride of the formula (I)′
and/or a mono- or bisacetylated or mono- or bisformylated form of formulae (I)″
in which
R 1 is optionally halogen- or C 1 -C 4 -alkoxy-substituted alkoxy having from 1 to 6 carbon atoms,
R 2 is C 1 -C 4 -alkyl-, and
R 3 is an acyl or formyl substituent,
which comprises reacting
an enamine of formula (II)
and/or a mono- or bisacetylated or mono- or bisformylated form of formula (H)″
with a chlorinating agent in the presence of at least one diluent wherein the diluent is selected from the group consisting of chlorobenzene and methylene chloride.
2. The process as claimed in claim 1 , wherein, in the formula (I),
R 1 is C 1 -C 4 -alkoxy,
R 2 is methyl, ethyl, or n- or i-propyl, and
R 3 is acyl or formyl.
3. The process as claimed in claim 1 , wherein the process is carried out at a temperature from −15° C. to 25° C.
4. The process as claimed in claim 1 , wherein the enamine of formula (II) has been obtained directly or as a precursor for an acetylated form of the formula (II)″ in a preceding process step from a compound of formula (III)
by reacting with ammonium formate, optionally in the presence of NH 3 , with ammonium acetate, optionally in the presence of NH 3 , with a mixture of formic acid and NH 3 and/or with a mixture of acetic acid and NH 3 in the presence of at least one diluent.
5. The process as claimed in claim 4 , wherein the enamine is not isolated.
6. The process as claimed in claim 1 , wherein the chlorinating agent is sulfuryl chloride.
7. A process for preparing a compound of formula (II)
in which
R 1 is optionally halogen- or C 1 -C 4 -alkoxy-substituted alkoxy having from 1 to 6 carbon atoms,
R 2 is C 1 -C 4 -alkyl-, and
which comprises reacting a compound of formula (III)
with ammonium formate, optionally in the presence of NH 3 , with ammonium acetate, optionally in the presence of NH 3 , with a mixture of formic acid and NH 3 and/or with a mixture of acetic acid and NH 3 in the presence of at least one diluent.
8. The process as claimed in claim 4 , wherein a compound of formula (III) is reacted with NH 3 in the presence of a catalytic amount of ammonium formate or ammonium acetate.
9. The process as claimed in claim 8 , wherein 0.1-0.8 mol of ammonium formate or ammonium acetate is used as said catalytic amount.
10. The process as claimed in claim 7 , wherein compounds of formula (III) are reacted with NH 3 in the presence of a catalytic amount of ammonium formate or ammonium acetate.
11. The process as claimed in claim 2 , wherein the reaction is carried out at a temperature from −15° C. and to 25° C.
12. The process as claimed in claim 2 , wherein the diluent is selected from the group consisting of chlorobenzene and methylene chloride.
13. The process as claimed claim 1 , wherein the enamine of formula (II) has been obtained directly or as a precursor for an acetylated form of the formula (II)″ in a preceding process step from a compound of formula (III)
by reacting with ammonium formate, optionally in the presence of NH 3 , with ammonium acetate, optionally in the presence of NH 3 , with a mixture of formic acid and NH 3 and/or with a mixture of acetic acid and NH 3 in the presence of at least one diluent.
14. A process of claim 1 , wherein no auxiliary base is added in said process.
15. The process as claimed in claim 1 , wherein R 2 is methyl.
16. The process as claimed in claim 1 , wherein the process is carried out at a temperature from −10° C. to 0° C.