1,2-Dichloroethane → (cis) (4-Bromothiazol-2-yl) (2,6-dimethylmorpholino)methanone

Temperature

0 °C

To a solution of 4-bromothiazole-2-carboxylic acid (prepared according to the procedure given in WO200857336, 1.35 g, 6.49 mmol) in DMF (15 ml) was added HOBT (1.09 g, 7.14 mmol) at room temperature followed by the addition of (2S,6R)-2,6-dimethylmorpholine (0.75 g, 0.8 ml, 6.49 mmol). The reaction mixture was cooled to 0° C. and to this were added EDC (1.86 gm., 9.73 mmol) and triethylamine (2.63 g, 3.62 ml, 26.00 mmol). 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) followed by brine (1×20 ml). The organic layer separated was dried over anhydrous sodium sulphate, filtered and concentrated at reduced pressure to get a crude product. The crude product was purified by column chromatography over silica gel (100-200 mesh) using 15% ethyl acetate in hexanes as an eluent to obtain the title compound (1.38 g, 69.7%). MS: m/z 306 (M+1)

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

ORD record

ord-528df6c938e148369efb3eb55c8e3033

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388196B2