Hydrochloric Acid → 2-Chloro-3-(trifluoromethyl)benzohydrazide

To a solution of 2-chloro-3-(trifluoromethyl)benzoyl chloride (15 g, 61.7 mmol, commercially available from e.g. Apollo) and DIPEA (12.94 ml, 74.1 mmol) in anhydrous dichloromethane (DCM) (200 ml) cooled to 0° C. in an ice bath was slowly added 1,1-dimethylethyl hydrazinecarboxylate (8.97 g, 67.9 mmol) under an atmosphere of argon and the mixture was allowed to reach steadily room temperature overnight. It was quenched with water (100 mL), the phases were separated and the aqueous extracted with DCM (2×50 mL). The combined organics were washed with brine (50 mL) and dried over MgSO4. The orange oil isolated (circa 25 g) was the impure BOC-protected hydrazide. It was then dissolved in 1,4-Dioxane (100 ml) and treated with HCl (4M in dioxane) (154 ml, 617 mmol) overnight at room temperature. The slurry was concentrated at the buchi to obtain a yellow solid which was triturated with Et2O to afford a white coloured solid, then applied to 4×10 g SCX cartridges, washed with MeOH and finally eluted with NH3 (2M in MeOH). The basic fractions were concentrated to afford the desired product in 3.5 g as a white solid.

1. customIt was quenched with water (100 mL)
2. customthe phases were separated
3. extractionthe aqueous extracted with DCM (2×50 mL)
4. washThe combined organics were washed with brine (50 mL)
5. dry with materialdried over MgSO4
6. customThe orange oil isolated (circa 25 g)
7. concentrationThe slurry was concentrated at the buchi
8. customto obtain a yellow solid which
9. customwas triturated with Et2O
10. customto afford a white coloured solid
11. washwashed with MeOH
12. washfinally eluted with NH3 (2M in MeOH)
13. concentrationThe basic fractions were concentrated

ORDレコード

ord-0c474065fbc448faaea84a636bf4775a

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08501946B2