Hydrogen Bromide → 2-Bromo-5-(trifluoromethyl)-1,3,4-thiadiazole

To 3 mL of 48% aqueous HBr was added 1.0 g (5.9 mmol) of 5-(trifluoromethyl)-1,3,4-thiadiazol-2-amine with stirring. The mixture was cooled in a salt ice-water bath, and 2.27 mL (44 mmol) of bromine was added slowly dropwise. The salt ice-water bath was replaced with an ice-water bath and a solution of 1.05 g (15 mmol) of sodium nitrite in 1.5 mL of water was added slowly dropwise. The reaction mixture was stirred for 1 h and then let warm to room temperature. The mixture was neutralized with 5M aqueous sodium hydroxide, and the resulting precipitate was filtered off. The filtrate was extracted with chloroform, and the extract was dried over magnesium sulfate before being concentrated to afford 750 mg (54%) of 2-bromo-5-(trifluoromethyl)-1,3,4-thiadiazole, 330 mg (1.4 mmol) of which was added to a solution of 240 mg (1.6 mmol) of (3S)-4,4-dimethyl-3-pyrrolidinol hydrochloride and 0.73 mL (4.2 mmol) of N,N-diisopropylethylamine in 5 mL of isopropanol. The reaction mixture was heated at reflux for 2 h, and then concentrated. The residue was purified by silica gel chromatography eluting with 0.3:9.7 methanol dichloromethane to afford 328 mg (88%) of (3S)-4,4-dimethyl-1-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]-3-pyrrolidinol. 1H NMR (300 MHz, DMSO-d6) δ 5.31 (d, J=5 Hz, 1H), 3.89-3.76 (m, 2H), 3.40-3.22 (m, 3H), 1.02 (s, 3H), 1.00 (s, 3H). Cl-LCMS m/z 268 (M+H).

1. temperatureThe mixture was cooled in a salt ice-water bath
2. customThe salt ice-water bath was replaced with an ice-water bath
3. stirringThe reaction mixture was stirred for 1 h
4. filtrationthe resulting precipitate was filtered off
5. extractionThe filtrate was extracted with chloroform
6. dry with materialthe extract was dried over magnesium sulfate
7. concentrationbefore being concentrated

ORDレコード

ord-6cd47abf51e944a586693df2aefddb68

出典データセット

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07402606B2