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To a nitrogen purged 12 liter 3-neck flask fitted with a mechanical stirrer and temperature probe was added THF (4.3 L) and 2,4-diaminobenzaldehyde (50 g, 0.37 mol, 1 equiv). After cooling the solution to −70° C. (dry ice/acetone bath), poly(4-vinylpyridine), which can be obtained form Aldrich, Milwaukee, Wis., 25% cross-linked, (210 g) was added. A solution of 4′-trifluoromethyl-biphenyl-2-carbonyl chloride (105 g, 0.37 mol, 1 equiv) in THF (1 L) was added at such a rate as to maintain the temperature below −60° C. The light orange reaction mixture was allowed to warm to room temperature over 4 hours to give a dark red reaction mixture. (HPLC analysis showed an 18:1 mixture of mono- (retention time (rt)=4.8 min) to di- (rt=3.1 min) acylated products along with 5% residual starting material (rt=18.8 min), (Zorbax SIL (150 mm) from Agilent Technologies, Palo Alto, Calif. 2 mL/min 90:10 hexanes/isopropanol, 0.1% diethylamine, 250 nm, 40° C.). The reaction was quenched with 1 N NaOH (450 mL) and allowed to stir overnight at 25° C. The reaction mixture was filtered and the solids were washed with ethyl acetate (5×200 mL) and the combined organic layers were concentrated in vacuo to give a brown oil. The oil was dissolved in CH2Cl2 (1.5 L) and silica gel (EM Science, Gibbstown, N.J., 230-400 mesh or 0.04-0.06 mm particle size) (410 g) and Darco G-60® (10 g, BNL Fine Chemicals and Reagents) were added. The slurry was stirred for 15 minutes and filtered. The silica was washed with CH2Cl2 (5×200 mL). The combined organic layers were concentrated in vacuo and the methylene chloride was displaced with 1:1 hexanes/diisopropylether. The precipitated product was collected by suction filtration and dried in air to give 4′-trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide (40 g, 30%, 43:1 mono:bis acylated by HPLC) as a light yellow solid.

1. customTo a nitrogen purged 12 liter 3-neck flask
2. customfitted with a mechanical stirrer
3. customcan be obtained form Aldrich, Milwaukee, Wis
4. addition, 25% cross-linked, (210 g) was added
5. temperatureto maintain the temperature below −60° C
6. customto give
7. customa dark red reaction mixture
8. additionan 18:1 mixture of mono- (retention time (rt)=4.8 min) to di- (rt=3.1 min)
9. customThe reaction was quenched with 1 N NaOH (450 mL)
10. filtrationThe reaction mixture was filtered
11. washthe solids were washed with ethyl acetate (5×200 mL)
12. concentrationthe combined organic layers were concentrated in vacuo
13. customto give a brown oil
14. stirringThe slurry was stirred for 15 minutes
15. filtrationfiltered
16. washThe silica was washed with CH2Cl2 (5×200 mL)
17. concentrationThe combined organic layers were concentrated in vacuo
18. filtrationThe precipitated product was collected by suction filtration
19. customdried in air