Reaktion #64560

Reaktionsgleichung

CH2Cl2

methyl 3-amino-4-chlorobenzoate

sodium nitrite

MeOH

→

Methyl 4-Chloro-3-hydrazinobenzoate

Lösungsmittel

HCl

H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added slowly via a dropping funnel
2. 2
   Filtrationthe mixture was filtered while cold
3. 3
   Temperaturwas also maintained at >0° C
4. 4
   SonstigePrecipitation of a cream-colored solid
5. 5
   workup.STIRRINGAfter being stirred at 0° C. for 0.5 hour
6. 6
   workup.WAITthe mixture was refrigerated overnight
7. 7
   SonstigeThe solid was collected on
8. 8
   Filtrationa filter
9. 9
   Sonstigetriturated with ether
10. 10
    Sonstigeto give
11. 11
    Sonstigeafter air-drying
12. 12
    Sonstigea portion of this hydrochloride salt was partitioned between 5% NaHCO3 (aqueous)
13. 13
    workup.ADDITIONa mixture of CH2Cl2 and ethyl acetate
14. 14
    Sonstigewhich was isolated by concentration of the organic phase
15. 15
    Sonstigeto give a cream-colored solid
16. 16
    SonstigeThis material was used immediately in the next reaction

Vorschrift

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.

Quelle