Facile approach for the synthesis of rivaroxaban using alternate synthon: reaction, crystallization and isolation in single pot to achieve desired yield, quality and crystal form

Sustainable Chemical Processes

Table 4 Trend data of yield and impurity profile of 1 in different reaction solvents/anti-solvents

Expt. no.	Reaction solvent	Base	Anti solvents	Yield (%)	HPLC purity (%)	Impurity profile by HPLC (%)
Expt. no.	Reaction solvent	Base	Anti solvents	Yield (%)	HPLC purity (%)	9	14	15	NP	11
1	DCM	TEA	–	NI	35.9	41	0.09	0.20	13.3	1.05
2	DMF	K₂CO₃	Water	60	98.84	0.56	0.02	0.10	0.16	0.12
3	DMF	TEA	Methanol	30	99.65	0.01	0.14	0.09	0.09	ND
4	DMF	TEA	Ethyl acetate	NI	99.62	0.07	0.14	0.08	0.02	ND
5	DMF	TEA	THF	20.0	99.70	0.07	0.05	0.08	0.02	ND
6	DMSO	TEA	Methanol	90.0	99.12	ND	0.14	0.22	0.14	ND
7	DMSO	TEA	IPA	NI	98.7	0.20	0.10	0.2	0.23	ND
8	DMSO	TEA	Acetic acid/water	75.0	97.1	0.04	0.13	0.10	1.78	ND
9	DMSO	TEA	Water	75.0	98.6	0.43	0.18	0.11	0.12	0.02
10	DMSO	TEA	Acetonitrile	69.1	99.85	0.01	0.06	0.03	0.01	0.02
11	DMSO	TEA	Acetonitrile	75.0	99.86	ND	0.07	0.02	0.02	ND
12	DMSO	DBU	Acetonitrile	75.1	99.70	ND	0.13	0.05	0.02	ND