Trifluoroacetic anhydride → HCID 23289220, compound

Temperature

2.5 °C

The thiourea obtained from the reaction of 3-methoxyphenyl isothiocyanate (5.02 g, 30.4 mmol) with piperazine (13.01 g, 151 mmol) in refluxing t-BuOH was cyclized with K3Fe(CN)6 and subsequently deprotected with molten pyridinium hydrochloride at about 160° C. according to the procedure described for Preparation 84, but without the chromatographic separation of the 5- and 7- isomers. The resulting 2-(piperazinyl)-benzothiazol-5-ol and -7-ol mixture (2.35 g, 10 mmol) was dissolved in trifluoroacetic acid (20 mL) and chilled to about 0-5° C. Trifluoroacetic anhydride (3.4 mL, 24 mmol) was added dropwise over several minutes. After stirring for about 3 h. at about 20° C. the mixture was concentrated in vacuo at about 35° C. and then redissolved in H2O (50 ml) with adjustment of the pH to 6-7 by careful addition of saturated aqueous K2CO3. The mixture was stirred for about 30 min. at about 20° C., diluted with H2O (60 mL) and extracted with 5% MeOH in CH2Cl2 (1×100 mL, 2→40 mL). Pooled organic extracts were dried over Na2SO4 (s) and concentrated in vacuo to afford a mixture of the 2-(4-trifluoroacetylpiperazin-1-yl) benzothiazol-5-ol and -7-ol isomers as a foamy solid (2.12 g; GC-MS m/z 331). The isomers were resolved by flash chromatography on silica (35% EtOAc/hexanes) to yield 820 mg of the pure 2-(4-trifluoroacetyl-piperazin-1-yl)benzothiazol-7-ol as the faster eluting isomer.

1. customdescribed for Preparation 84
2. customwithout the chromatographic separation of the 5- and 7- isomers
3. concentrationwas concentrated in vacuo at about 35° C.
4. dissolutionredissolved in H2O (50 ml) with adjustment of the pH to 6-7 by careful addition of saturated aqueous K2CO3
5. stirringThe mixture was stirred for about 30 min. at about 20° C.
6. additiondiluted with H2O (60 mL)
7. extractionextracted with 5% MeOH in CH2Cl2 (1×100 mL, 2→40 mL)
8. dry with materialPooled organic extracts were dried over Na2SO4 (s)
9. concentrationconcentrated in vacuo
10. customto afford

ORD record

ord-cf7eba7212364f9a9df408e4b6779af6

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06130217