Isopropylamine → 4-Bromo-N-isopropylbenzamide

Temperature

0 °C

A solution of 4-bromobenzoic acid (4.00 g, 19.9 mmol, Aldrich: Cat. #108510) and thionyl chloride (10.0 mL, 137 mmol) was heated by microwave irradiation at 100° C. for 1 h, turning the heterogeneous solution to a homogeneous solution. The volatiles were removed in vacuo and the residue was azeotropically washed with dry acetonitrile several times (20 mL×4) to remove excess thionyl chloride. The residue was dissolved in anhydrous methylene chloride (40 mL) and cooled to 0° C. prior to the addition of 2-propanamine (8.0 mL, 94 mmol, 99.5% pure Aldrich [75-31-0]). After 1 hour, the reaction mixture was diluted with methylene chloride (20 mL) and quenched with H2O (5 mL). The layers were separated and the organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to afford the desired product (4.50 g, 93% yield) which was used directly in the next step without further purification. LCMS (M+H)+: m/z=242/244.

1. customThe volatiles were removed in vacuo
2. washthe residue was azeotropically washed with dry acetonitrile several times (20 mL×4)
3. customto remove excess thionyl chloride
4. dissolutionThe residue was dissolved in anhydrous methylene chloride (40 mL)
5. customquenched with H2O (5 mL)
6. customThe layers were separated
7. washthe organic layer was washed with H2O (1×5 mL), saturated NaHCO3 (1×5 mL), H2O (1×5 mL), 1 N HCl (3×5 mL), H2O (1×5 mL), and brine (5 mL)
8. dry with materialThe organic layer was dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-ea33984f99794a018b28da594b33619d

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691807B2