Imidazole → Benzoic acid, 4-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-

Participants

Reaction Steps

The photolabile linker was prepared as described by Holmes et al. in J. Org. Chem., 60: 2318-2319 (1995). 2-methoxy-4-acetylphenol was treated with Br—(CH2)3—CO2CH3 and K2CO3 in DMF and the product was reacted with excess hydroxylamine hydrochloride/pyridine/H2O. The oxime formed was reduced with H2/Pd/C in acetic acid and the resulting amine trifluoroacetylated with the anhydride in pyridine. The product was crystallized from ethanol water (80% four steps). The product was nitrated with concentrated nitrous acid in acetic acid (86%). The protecting groups were removed by reflux in NaOH/MeOH/H2O and the crude product was reacted with Fmoc chloride (81%). 4-[(tert-butyldimethylsiloxy)methyl]benzoic acid (TBDMS-HMBA) was prepared as described by Kita et al. in J. Org. Chem., 51: 4150-4158 (1986). 4-(hydroxymethyl)-benzoic acid (0.76 g, 5 mmol) was reacted with tert-butyldimethylsilyl chloride (2.29 g, 15 mmol) and imidazole (2.04 g, 30 mmol) in dry DMF (12 mL). Aqueous workup gave (0.86 g) 65% yield of the 4-[(tert-butyldimethylsiloxy)methyl]benzoic acid with melting point 157-159° C., δppm 8.06 (d, J=8 Hz); 7.39(d, J=8 Hz); 4.78 (s); 0.94 (s); 0.11 (s).

Provenance & Evidence