Processes for the preparation of thietanamine

A compound of formula III-1, III-2, III-3a, III-3b, III-3c or III-4

• wherein R1 is C1-C8alkyl, C1-C8haloalkyl, phenyl or phenyl substituted by one to five groups independently selected from halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl and C1-C4alkoxy;
• R3 and R4 are independently H, C1-C8alkyl or C1-C8haloalkyl, C1-C8alkoxy, phenyl or phenyl substituted by one to five groups independently selected from halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl and C1-C4alkoxy, provided R3 is not tert-butyloxy when R12 is H in the compound of formula (III-3a);
• each R8 is independently halogen, CN, NO2, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy;
• n is 0 to 4;
• A6 and A7 are independently C(R9)R10 or NR11 providing that both A6 and A7 are not NR11, or A6 and A7 are together —C(R9)═C(R9)—;
• each R9, R10 and R11 are independently hydrogen, C1-C8alkyl or C1-C8haloalkyl;
• R12 is hydrogen or —C(═O)—R4.

A process for the preparation of a compound of formula I

• comprising
• 1) reacting a compound of formula II
• with a source of cyanide in the presence of water to give a compound of formula XI
• 2) hydrolysing the compound of formula XI, or reacting the compound of formula XI with acetaldehyde hydroxime in the presence of a metal catalyst such as InCl3 to give a compound of formula XII
• 3) reacting the compound of formula XII with a brominating agent such as a compound of formula XIII in the presence of methoxide, or t-butoxide under anhydrous conditions or in
• the presence of tetra-n-butylammonium bromide under aqueous conditions
• to give a compound of formula XIV, XV or XVI respectively
• 4) hydrolysing the product of step 3 to give a compound of formula I.

A process for the preparation of a compound of formula I

• comprising
• 1) reacting a compound of formula II
• with a source of cyanide in the presence of water to give a compound of formula XI
• 5) hydrolysing the compound of formula XI to give a compound of formula XVII
• 6) reacting the compound of formula XVII with hydroxylamine to give a compound of formula XVIII
• 7) reacting the compound of formula XVIII with a dehydrating agent such as a compound of formula XIX in the presence of methanol
• to give a compound of formula XIV
• 8) hydrolysing the compound of formula XIV to give a compound of formula I.

A process for the preparation of a compound of formula I

• comprising
• 1) reacting a compound of formula II
• with a source of cyanide in the presence of water to give a compound of formula XI
• 5) hydrolysing the compound of formula XI to give a compound of formula XVII
• 9) converting the compound of formula XVI to a compound of formula I by reacting the compound of formula XVI with hydrazoic acid or by reacting the compound of formula XVI with diphenylphosphoryl azide followed by reaction with an alcohol to obtain the corresponding ester, following by deprotecting to provide the compound of formula I.