Riluzole → 3-(2-Acetamidoethyl)-2-imino-6-trifluoromethoxybenzothiazoline

HRID 1111369

Reaction equation

[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:7][C:5]=2[N:6]=1.Cl[CH2:17][CH2:18][NH:19][C:20](=[O:22])[CH3:21].[I-].[Na+]>C(C(C)=O)C>[C:20]([NH:19][CH2:18][CH2:17][N:6]1[C:5]2[CH:7]=[CH:8][C:9]([O:11][C:12]([F:15])([F:13])[F:14])=[CH:10][C:4]=2[S:3][C:2]1=[NH:1])(=[O:22])[CH3:21]

Participants

Conditions

Temperature: 20 °C

Procedure

2-Amino-6-trifluoromethoxybenzothiazole (9.4 g), N-(2-chloroethyl)acetamide (9.7 g) and sodium iodide (13.5 g) in methyl ethyl ketone (30 cc) are heated for 40 hours to boiling. After cooling to a temperature in the region of 20° C., the reaction medium is added to distilled water (200 cc), treated with 1N sodium hydroxide (40 cc) and then extracted with ethyl acetate (200 cc). After drying over magnesium sulphate and then concentration to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa), the residue is purified by chromatography on a silica column with a mixture of ethyl acetate and methanol (90:10 by volume) as eluent. 3-(2-Acetamidoethyl)-2-imino-6-trifluoromethoxybenzothiazoline (2.7 g) is obtained, which product is converted to a hydrochloride subliming at about 180° C.

Workup

additionthe reaction medium is added
distillationto distilled water (200 cc)
additiontreated with 1N sodium hydroxide (40 cc)
extractionextracted with ethyl acetate (200 cc)
dry with materialAfter drying over magnesium sulphate
concentrationconcentration to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa)
customthe residue is purified by chromatography on a silica column with a mixture of ethyl acetate and methanol (90:10 by volume) as eluent

Sources & evidence

ORD record: ord-5adc69eb76704e68ba0a32ca3e20db64
Source dataset: uspto-grants-1990_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04980356

Linked notes

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