1,2-Dichloroethane → 3-Oxa-8-azabicyclo[3.2.1]octan-8-yl(4-bromothiazol-2-yl)methanone

Temperature

0 °C

To a solution of 4-bromothiazole-2-carboxylic acid (prepared according to the procedure given in WO 2008/57336, 1.4 g, 6.73 mmol) in DMF (15 ml) was added HOBT (1.13 g, 7.40 mmol) at room temperature, followed by the addition of 3-oxa-8-azabicyclo[3.2.1]octane (prepared according to the procedure given in WO 2010/120854, 0.76 g, 6.69 mmol). Reaction mixture was cooled to 0° C. and to this were added EDC (1.93 g, 10.10 mmol) and triethylamine (3.40 g, 4.69 ml, 33.60 mmol). Reaction mixture was stirred at room temperature for 15 hr. The progress of reaction was monitored by TLC. The reaction mixture was concentrated under reduced pressure. The residue so obtained was taken in ethyl acetate (150 ml) and washed with saturated sodium bicarbonate solution (1×40 ml), brine (1×20 ml). The organic layers separated were dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to get a crude product. This crude product was purified by column chromatography over silica gel (100-200 mesh) using 2.5% methanol in DCM as an eluent to obtain the title compound (0.35 g. 17.15%). MS: m/z 304 (M+1).

1. customprepared
2. customReaction mixture
3. customReaction mixture
4. customThe progress of reaction
5. concentrationThe reaction mixture was concentrated under reduced pressure
6. customThe residue so obtained
7. washwashed with saturated sodium bicarbonate solution (1×40 ml), brine (1×20 ml)
8. customThe organic layers separated
9. dry with materialwere dried over anhydrous sodium sulphate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customto get a crude product
13. customThis crude product was purified by column chromatography over silica gel (100-200 mesh)

ORD record

ord-52f74d84ee144d52ba60b916baec9ff1

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388196B2