2,2-dimethylbutanal

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Examples of the aldehyde of the general formula (1) include trimethylacetaldehyde, 2,2-dimethylbutanal, 2-ethyl-2-methylbutanal, 2,2-dimethyl-4-pentenal, 2,2-dimethylpentanal, 2,2-dimethylpenta-3,4-dienal and the like. Particularly, trimethylacetaldehyde (boiling point 74° C. at 730 mmHg) and 2,2-dimethy-4-pentenal (boiling point 124° C. at 760 mmHg) are preferable examples of the invention because the both substances themselves and the corresponding alcohols formed at the preparation of vitamin A aldehyde as side products have lower boiling points, so that these materials can be easily removed from the reaction mixtures at lower temperatures after the completion of the reaction.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 0.493 g 1-(5-methoxy-3-methyl-1-benzofuran-2-yl)-2,2-dimethylpropan-1-one from Step A Example 1 in 20 mL anhydrous THF at −78° C. under nitrogen was added 2.0 mL 2 M LDA in heptane, THF, and ethylbenzene. After 50 minutes, 0.40 g 2,2-dimethylbutanal was added. Remove the cooling bath and let the reaction mixture warm up to room temperature. After 70 minutes, the reaction was quenched by adding 2 mL saturated ammonium chloride and the reaction mixture was evaporated under reduced pressure to remove solvents. Dilute the residue with ether, wash with 1 M HCl (2×) and saturated brine, dry over anhydrous Na2SO4, and evaporate to give a crude product. It was purified on RP-HPLC using 65˜100% MeCN in water without TFA to give the title compound as colorless solid after lyophilization. 1H NMR (CDCl3, 500 MHz) 7.44 (d, 9.1 Hz, 1H), 7.20 (d, 2.0 Hz, 1H), 7.10 (dd, 2.5 & 9.1 Hz, 1H), 3.86 (s, 3H), 3.58 (dd, 1.6 & 10.6 Hz, 1H), 3.29˜3.34 (m, 1H), 2.90˜2.95 (m, 1H), 1.51˜1.59 (m, 1H), 1.39˜1.46 (m, 1H), 1.40 (s, 9H), 1.02 (s, 3H), 1.01 (s, 3H), 0.92 (t, 7.6 Hz, 3H). LC-MS: 4.47 min. (m/Z=329.3, 369.2, 347). A faster-eluting isomeric side-product was also isolated during purification and was identified as 1-[2-(1-hydroxy-2,2-dimethylpropyl)-5-methoxy-1-benzofuran-3-yl]-3,3-dimethylpentan-2-one. 1H NMR (CDCl3, 500 MHz) 7.30 (d, 9.0 Hz, 1H), 6.84 (dd, 2.5 & 8.9 Hz, 1H), 6.75 (d, 2.5 Hz, 1H), 4.44 (s, 1H), 4.07 (AB d, 18.5 Hz, 1H), 4.04 (AB d, 18.5 Hz, 1H), 3.78 (s, 3H). 1.74 (q, 7.6 Hz, 2H), 1.263 (s, 3H), 1.260 (s, 3H), 0.99 (s, 9H), 0.91 (t, 7.4 Hz, 3H). LC-MS: 3.95 min. (m/Z=369.3=M+Na, 329.3,). Remove the cooling bath After 70 minutes the reaction was quenched by adding 2 mL saturated ammonium chloride the reaction mixture was evaporated under reduced pressure to remove solvents Dilute the residue with ether wash with 1 M HCl (2×) and saturated brine dry over anhydrous Na2SO4 evaporate to give a crude product It was purified on RP-HPLC