5,5-dimethylcyclohexane-1,3-dione

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:

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

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

Procedure: Bromine (0.51 mL, 10 mmol) was added dropwise to a solution of 5,5-dimethylcyclohexane-1,3-dione (1.4 g, 10 mmol) in AcOH (20 mL) at r.t. The reaction mixture was stirred for 2 h and then the product was isolated by filtration. The precipitate was washed with Et2O (2×100 mL) and then dried in vacuo give the title compound in quantitative yield as a light brown solid, which was used without further purification. LCMS (ES+) 218.9 (M+H)+. the product was isolated by filtration The precipitate was washed with Et2O (2×100 mL) dried in vacuo

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

Procedure: A stirred solution of p-anisaldehyde (1.74 mL, 14.3 mmol) and malononitrile (0.90 mL, 14.28 mmol) in 75 mL of 95% EtOH at RT was treated with a few drops of piperidine and after about 5 min, a yellow precipitate was formed and the mixture was stirred for another 10 min after which 5,5-dimethylcyclohexan-1,3-dione (2.00 g, 14.3 mmol) was added as a solid in one portion. The stirred suspension became a solution after about 5 min. After about 2 h a white precipitate was formed and TLC analysis showed complete reaction. The precipitate was filtered and washed with cold 95% EtOH then dried under vacuum, resulting in 3.71 g (81%) of the title compound as a white solid, mp 197-200° C. 1H NMR (DMSO-d6): 7.04 (d, 2H), 6.96 (bs, 2H), 6.83 (d, 2H), 4.11 (s, 1H), 3.71 (s, 3H), 2.49 (m, 2H), 2.15 (m, 2H), 1.03 (s, 3H), 0.94 (s, 3H). a yellow precipitate was formed was added as a solid in one portion after about 5 min After about 2 h a white precipitate was formed reaction The precipitate was filtered washed with cold 95% EtOH then dried under vacuum

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-amino-2-methacrolein (8.5 g., 0.1 mol.) and dimedone (14 g., 0.1 mol.) was treated with triethylamine (5 ml.) and ammonium acetate (0.1 g.) and heated in an oil bath at 120° C with stirring for 20 hours. The cooled reaction mixture was diluted with 2N HCl (50 ml.) and extracted with ethyl acetate (2 × 50 ml.) and the extracts discarded. The aqueous solution was adjusted to pH 10.0 with sodium bicarbonate and extracted with ethyl acetate (3 × 50 ml.). The combined extracts were dried (MgSO4) and the solvent removed to give a residual oil which was distilled to give the title compound as a colorless oil (7.8 g., 40% b.p. 80°/0.2 mm Hg. (RT = 2 min. 2% OV17, T=150°). The cooled reaction mixture extracted with ethyl acetate (2 × 50 ml.) extracted with ethyl acetate (3 × 50 ml.) The combined extracts were dried (MgSO4) the solvent removed to give a residual oil which was distilled

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

Procedure: Using the procedure described in Example III and starting with 3.00 g (0.0130 mol) of 2-4'-methylphenyl)-5,5-dimethyl-1,3-cyclohexanedione, 2.69 g (0.0098 mol) of palmitoyl chloride, 2.63 g (0.0260 mol) of triethylamine, and 30 ml of methylene chloride, 3.1 g (67% yield) of a clear, colorless oil was obtained as the desired product.

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

Procedure: 14.0 g (0.1 mol) of dimedone were dissolved in 200 ml of THF. 3.8 g (0.1 mol) of NaBH4 and 5 mmol of CeCl3 dissolved in 50 ml of THF were then added at -30° C. The mixture was stirred at room temperature for another 2 hours and was hydrolyzed at 0° C. by means of methanol/water. The organic phase was separated off and the solvent was removed. The residue was extracted with ethanol and unreacted dimedone was removed by crystallization. This gave 11.5 g (80%) of 5,5-dimethylcyclohexane-1,3-diol. were then added at -30° C The organic phase was separated off the solvent was removed The residue was extracted with ethanol and unreacted dimedone was removed by crystallization

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

Procedure: 3-Cyano-3-{3-cyclohexyl-2-[(morpholine-4-carbonyl)-amino]-propionylamino}-pyrrolidine-1-carboxylic acid (2-propen-1-yl) ester (1.35 g, 2.93 mmol, 1.00 equiv) was dissolved in 35 mL of CH2Cl2 along with dimedone (3.30 g, 23.5 mmol, 8.03 equiv). Pd(PPh3)4 (0.25 g, 0.22 mmol, 0.07 equiv) was added and the suspension was stirred at room temperature for 3.5 h. The reaction mixture was concentrated and taken up into EtOAc (100 mL) and extracted with 1 N HCl (2×50 mL). Concentration of the organic phase and purification of the crude mixture by reverse-phase HPLC provide the product as two separate diastereomers; MS, m/z 500=M+1. The reaction mixture was concentrated extracted with 1 N HCl (2×50 mL) Concentration of the organic phase and purification of the crude mixture by reverse-phase HPLC provide the product as two separate diastereomers