Acetic Acid → HCID 11175556, compound

Participants

Reaction Steps

2-(Benzyloxy)-5-bromobenzenecarbaldehyde (9) (20 g, 69 mmol) was dissolved in MeOH (150 mL) and was then followed by the addition of potassium cyanide (20.1 g, 308 mmol). Acetic acid (6.3 mL, 109 mmol) was added dropwise over 20 min at ambient temperature. The resulting mixture was stirred at ambient temperature for 3 h. Acetic acid (2 mL) was added and the mixture was stirred for an additional 1 h. Additional acetic acid (30 mL) was added and the mixture was diluted with H2O (60 mL). After concentration at reduced pressure, the aqueous residue was extracted with EtOAc (3×100 mL). The combined organics were washed with brine and dried over MgSO4. Filtration and concentration left a pale yellow oil, which was without further purification. The title compound (10) could be isolated in pure form by gradient column chromatography (10 to 20% EtOAc in Hexanes). 1H NMR (400 MHz, CDCl3) 7.53 (d, 1H); 7.24 (m, 6H); 6.86 (d, 1H); 5.52 (d, 1H); 5.13 (s, 2H); 3.38 (d, 1H). MS 199, 201(M-Bn-CN). HPLC 20.40 min. (95% H2O:5% CH3CN)+0.1% TFA to (10% H2O:90% CH3CN)+0.1% TFA over 22 min on a Vyadec 218TP54 C18 Column Step (c): Preparation of methyl 2-[2-(benzyloxy)-5-bromophenyl]-2-hydroxyacetate Crude 2-[2-(benzyloxy)-5-bromophenyl]-2-hydroxyacetonitrile (10), from above, was dissolved in anhydrous dioxane (25 mL), ether (25 mL) and MeOH (6 mL). After cooling the mixture to 0° C., it was saturated with HCl gas and warmed to ambient temperature. A precipitate formed and the mixture was stirred for 1.5 h. [If the mixture became too viscous to stir, anhydrous ether was added]. The reaction mixture was diluted with ether (200 mL) and filtered. The colorless solid was washed with ether and used as is.

Provenance & Evidence