Methanol → Methyl 4-chloro-3-hydrazinylbenzoate

A solution of 11.9 g (63.9 mmole) of methyl 3-amino-4-chlorobenzoate (prepared as in Step A) was maintained at -5° to +5° C. and subjected to vigorous mechanical stirring as a solution of 4.41 g (63.9 mmole) of sodium nitrite in 19.3 mL of H2O was added slowly via a dropping funnel. Stirring was continued at this temperature for 1 hour, and the mixture was filtered while cold. The filtrate was immediately added to a rapidly stirred solution of 28.8 g (128 mmole) of stannous chloride dihydrate in 37.3 mL of concentrated HCl, which was also maintained at >0° C. Precipitation of a cream-colored solid began at once. After being stirred at 0° C. for 0.5 hour, the mixture was refrigerated overnight. The solid was collected on a filter and triturated with ether to give, after air-drying, approximately 22 g of cream-colored solid (mp 218°-220° C.), which was stored in the freezer. As needed, a portion of this hydrochloride salt was partitioned between 5% NaHCO3 (aqueous) and a mixture of CH2Cl2 and ethyl acetate to liberate the title compound as the free base, which was isolated by concentration of the organic phase to give a cream-colored solid, homogeneous by TLC (95:5 CH2Cl2 --MeOH); mass spectrum (EI) m/e 200 (M+). This material was used immediately in the next reaction.

1. additionwas added slowly via a dropping funnel
2. filtrationthe mixture was filtered while cold
3. temperaturewas also maintained at >0° C
4. customPrecipitation of a cream-colored solid
5. stirringAfter being stirred at 0° C. for 0.5 hour
6. waitthe mixture was refrigerated overnight
7. customThe solid was collected on
8. filtrationa filter
9. customtriturated with ether
10. customto give
11. customafter air-drying
12. customa portion of this hydrochloride salt was partitioned between 5% NaHCO3 (aqueous)
13. additiona mixture of CH2Cl2 and ethyl acetate
14. customwhich was isolated by concentration of the organic phase
15. customto give a cream-colored solid
16. customThis material was used immediately in the next reaction

ORD-Eintrag

ord-851541690cf84f008c0468cc99e613fc

Quelldatensatz

uspto-grants-1995_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05411980