ethyl 6-methyl-3-oxoheptanoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 6-methyl-3-oxoheptanoate (1.08 g, 5.53 mmol, 1.25 eq.) obtained in Example 97a) and 4-azido-N-ethylbenzamide (0.842 g, 4.43 mmol) were dissolved in ethanol (25 ml), sodium ethoxide (418 mg, 5.53 mmol, 1.25 eq.) was added, and the mixture was stirred at room temperature for 30 min and at 60° C. for 17 hr. 2% Aqueous sodium carbonate solution (20 ml) was added to the reaction mixture, ethanol was evaporated, and the residue was diluted with water (20 ml) and washed with ethyl acetate-hexane (2:1, 40 ml). The organic layer was extracted with 2% aqueous sodium carbonate solution (20 ml). The aqueous layers were combined, acidified (pH<3) with 6N hydrochloric acid, and stood still at 0° C. The precipitate was collected by filtration and washed with cold water and dried to give the title compound as a grayish white powder (1.41 g, 4.27 mmol, 96.3%). was evaporated the residue was diluted with water (20 ml) washed with ethyl acetate-hexane (2:1, 40 ml) The organic layer was extracted with 2% aqueous sodium carbonate solution (20 ml) stood still at 0° C The precipitate was collected by filtration washed with cold water dried

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of diazo-acetic acid ethyl ester (555 mg, 4.86 mmol) in dichloromethane (8 mL) was treated with tin (II) chloride (88 mg, 0.463 mmol) and stirred vigorously at 25° C. A solution of 4-methyl-pentanal (464 mg, 4.63 mmol) in dichloromethane (2 mL) was added to the mixture dropwise over 10 min resulting in gas evolution. After the nitrogen evolution ceased (approximately 1 h), the reaction was extracted with brine and diethyl ether (2×80 mL). The organic layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by flash column chromatography (ISCO RediSep column, 0 to 7% ethyl acetate in hexanes) to afford the desired product, 6-methyl-3-oxo-heptanoic acid ethyl ester (478 mg, 55%), as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ: 0.89 (6H, d, J=6.3 Hz), 1.26-1.29 (4H, m), 1.48-1.57 (2H, m), 2.53 (2H, t, J=7.4 Hz), 3.42 (2H, s), 4.18 (2H, quartet, J=7.6 Hz). resulting in gas evolution (approximately 1 h) the reaction was extracted with brine and diethyl ether (2×80 mL) dried over sodium sulfate filtered concentrated in vacuo The crude material was purified by flash column chromatography (ISCO RediSep column, 0 to 7% ethyl acetate in hexanes)