Improved one-pot synthesis of N, N-diisopropyl-3-(2-Hydroxy-5-methylphenyl)-3-phenyl propanamide; a key intermediate for the preparation of racemic Tolterodine

Sustainable Chemical Processes

Table 1 Screening of solvent for the synthesis of compound 4

Entry	Coumarin	Amine	Solvent	Temparature	Yield (%)^c
1.	2	DIPA^a	DCM	Reflux	No reaction
2.	2	DIPA	THF	Reflux	No reaction
3.	2	DIPA	ACN	Reflux	No reaction
4.	2	DIPA	ACN	Sealed tube^b	15
5.	2	DIPA	Methanol	25-30°C	15
6.	2	DIPA	Methanol	Reflux	15
7.	2	DIPA	Ethanol	Reflux	10
8.	2	DIPA	Toluene	Reflux	30
9.	2	DIPA	Diisopropylether	25-30°C	53

^aN.N-diisopropylamine (DIPA), for all the above reactions 5 mole equivalents of DIPA used. ^bpressure reaction performed at 110°C. ^cisolated yields.