Citric Acid → tert-Butyl 5'-bromo-3'h-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

温度

-20 °C

4-bromo-2-(chloromethyl)-1-iodobenzene (500 g, 1.509 moles) was dissolved in tetrahydrofuran (3750 mL) and cooled to −20° C. i-PrMgCl—LiCl (1.3M solution in THF) (1275 ml, 1.66 moles) was added at less than −15° C. The reaction mixture was cooled to −20° C. 3-oxo-azetidine-1-carboxylic acid, tert-butyl ester (310 g, 1.81 moles), as a solution in tetrahydrofuran (750 mL), was added. The reaction was warmed to room temperature over 90 minutes, and then stirred overnight. 1M Aqueous citric acid solution (2 L) was added, followed by tert-butylmethylether (2 L). The mixture was shaken. The organic phase was separated, dried over anhydrous magnesium sulphate, filtered and evaporated to dryness to give an orange oil. The oil was dissolved in ethanol (2.5 L) and the solution diluted with water (1 L). The mixture stood at room temperature, overnight. The resulting crystals of tert-butyl 5′-bromo-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate were filtered under reduced pressure and dried under vacuum at 50° C., giving 290 g. 1H NMR (CDCl3) δ ppm: 1.49 (9H, s), 4.15 (2H, d), 4.34 (2H, d), 5.11 (2H, s), 7.38 (2H, m), 7.56 (1H, d).

1. additionwas added at less than −15° C
2. temperatureThe reaction was warmed to room temperature over 90 minutes
3. stirringThe mixture was shaken
4. customThe organic phase was separated
5. dry with materialdried over anhydrous magnesium sulphate
6. filtrationfiltered
7. customevaporated to dryness
8. customto give an orange oil
9. waitThe mixture stood at room temperature, overnight
10. filtrationThe resulting crystals of tert-butyl 5′-bromo-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate were filtered under reduced pressure
11. customdried under vacuum at 50° C.
12. customgiving 290 g

ORDレコード

ord-beaafe6a3ea04e07904db9528f362315

出典データセット

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09200003B2