3-methoxy-3-oxopropanoic acid

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

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

Conditions: temp:50.01; pressure:0.00; stir:

Procedure: The product mixture was cooled to 25 °C. Filtered through a pad of celite "The celite was washed with ethyl acetate (3 x 1 mL)." The filtrate was concentrated under reduced pressure A 0.07 M stock solution of the internal standard ethylene carbonate (0.70 mL in CDCl3) was added.

Conditions: temp:25.01; pressure:0.00; stir:

Procedure: The product mixture was cooled to 25 °C. Filtered through a pad of celite "The celite was washed with ethyl acetate (3 x 1 mL)." The filtrate was concentrated under reduced pressure A 0.07 M stock solution of the internal standard ethylene carbonate (0.70 mL in CDCl3) was added.

Conditions: temp:50.01; pressure:0.00; stir:

Procedure: The product mixture was cooled to 25 °C. Filtered through a pad of celite "The celite was washed with ethyl acetate (3 x 1 mL)." The filtrate was concentrated under reduced pressure A 0.07 M stock solution of the internal standard ethylene carbonate (0.70 mL in CDCl3) was added.

Conditions: temp:25.01; pressure:0.00; stir:

Procedure: The product mixture was cooled to 25 °C. Filtered through a pad of celite "The celite was washed with ethyl acetate (3 x 1 mL)." The filtrate was concentrated under reduced pressure A 0.07 M stock solution of the internal standard ethylene carbonate (0.70 mL in CDCl3) was added.

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

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

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

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

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

Procedure: To a suspension of magnesium ethoxide (10.82 g, 94.61 mmol) in 1,4-dioxane (100 mL) was added methyl hydrogen malonate (25.0 g, 189 mmol) in 1,4-dioxane (100 mL). The resulting slurry was stirred overnight. The mixture was concentrated in vacuo. In a separate flask, lauric acid (28, 20.85 g, 104.1 mmol) was dissolved in 1,4-dioxane (50 mL) and a solution of CU (16.88 g, 104.1 mmol) in 1,4-dioxane (150 mL) was added at room temperature. The resulting solution was stirred overnight. The mixture was then transferred to the methyl magnesium malonate flask. The resulting suspension was refluxed overnight. The mixture was concentrated in vacuo. The residue was redissolved in DCM (300 mL) and filtered through a silica plug (10 g). The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (360 g RediSep column, eluting with a gradient of 0% through 30% ethyl acetate/hexanes over 80 min, 100 mL/min) to afford product 29 (17 g, 61%) as a pale yellow syrup. The mixture was concentrated in vacuo The resulting solution was stirred overnight The resulting suspension was refluxed overnight The mixture was concentrated in vacuo The residue was redissolved in DCM (300 mL) filtered through a silica plug (10 g) The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (360 g RediSep column eluting with a gradient of 0% through 30% ethyl acetate/hexanes over 80 min

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

Procedure: Synthesis in analogy to the General Method 1 starting from (3aS,4R,7aS)-4-hydroxy-4-m-tolylethyny-octahydro-indole-1-carboxylic acid methyl ester and malonic acid monomethyl ester to yield (3aR,4S,7aR)-1-(methoxycarbonyl)-4-(m-tolylethynyl)octahydro-1H-indol-4-yl methyl malonate. MS [M+H]=414; RT=1.24 min; UPLC Method I