Acetic Acid → HCID 22250413, compound

To a mixture of 2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester (100 mg, 0.515 mmol) and chloroiodomethane (0.075 ml, 1.03 mmol) in 1 ml of THF was added a solution of LDA in THF (2M, 0.57 ml, 1.13 mmol) dropwise at −78 C over 15 min. The reaction mixture was stirred at −78 C for 10 min. A solution of acetic acid (0.75 ml) in THF (5 ml) was added dropwise over 5 min at −78 C. The resulting solution was stirred at the same temperature for additional 10 min. and was then partitioned between ethyl acetate and water. The organic layer was washed with aqueous sodium bicarbonate, brine, dried over MgSO4 and concentrated in vacuo to give the crude 2-chloro-1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-ethanone as a light brown liquid. The crude product was dissolved in EtOH (1.5 ml). Thiourea (76 mg, 1 mmol) was added followed by addition of TEA (0.14 ml, 1 mmol). The solution was heated at 80 C for 6 h. After removal of ethanol, the reaction mixture was taken into ethyl acetate and aqueous sodium bicarbonate. The organic layer was washed with 0.5 N HCl. After separation, the aqueous layer was adjusted to pH 9 with sodium carbonate, and extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried over MgSO4 and concentrated to give 4-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-thiazol-2-ylamine as a brown solid, 37 mg (0.16 mmol, 31% yield). 1H NMR (CDCl3) δ 7.46 (dd, 1H), 7.04 (s, 1H), 6.75-6.83 (m, 2H), 5.33 (br s, 2H), 4.23-4.34 (m, 4H); LC/MS m/z 235 (M+H)+.

1. stirringThe resulting solution was stirred at the same temperature for additional 10 min.
2. customwas then partitioned between ethyl acetate and water
3. washThe organic layer was washed with aqueous sodium bicarbonate, brine
4. dry with materialdried over MgSO4
5. concentrationconcentrated in vacuo

ORD record

ord-c36daf3e0aa24bcba5f415a5484a8aec

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968577B2