ethyl 2,2-diethoxyacetate

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:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 40 mL (224 mmol) of ethyl diethoxyacetate, 38 mL (536 mmol) of acetyl chloride and 0.11 g (0.45 mmol) of iodine are placed in a round-bottomed flask and heated at 50° C. for 24 hours. The reaction progress is monitored by NMR. The excess acetyl chloride is removed by evaporation under vacuum. 36.3 g (100%) of ethyl chloroethoxyacetate are obtained in the form of a liquid colored brown by the residual iodine. The excess acetyl chloride is removed by evaporation under vacuum

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20 mL (112 mmol) of ethyl diethoxyacetate, 16 mL (224 mmol) of acetyl chloride and 60 mg (0.2 mmol) of iodine are placed in a round-bottomed flask and heated at 50° C. for 24 hours. The reaction progress is monitored by NMR. The excess acetyl chloride is removed by evaporation under vacuum. 19 g (100%) of ethyl chloroethoxyacetate are obtained in the form of a liquid colored brown by the residual iodine. The excess acetyl chloride is removed by evaporation under vacuum

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 250 mL round bottom flask, 9.5 mL of n-butyl lithium (2.5 M solution in hexane, 23.8 mmol) was added via a syringe to a pre-cooled solution (−78° C.) of 2-(2-methylbut-3-yn-2-yloxy)-tetrahydro-2H-pyran 2 (4.0 g, 23.8 mmol) in 100 mL of Et2O. The resulting solution was stirred for 30 min at −78° C., then ethyl 2,2-diethoxyacetate (4.9 g, 27.7 mmol) was added with a syringe, and the stirring continued for 12 hours. The reaction mixture was poured in an ice-cold saturated aqueous solution of NH4Cl. The aqueous layer was extracted with Et2O (3×50 mL). The organic solvent was separated with a separating funnel and dried with anhydrous MgSO4. The solvent was removed under reduced pressure and the resulting pale yellow oil was purified by radial chromatography (stationary phase silica gel, hexane/AcOEt 90:10) to provide 1,1-diethoxy-5-methyl-5-(tetrahydro-2H-pyran-2-yloxy)hex-3-yn-2-one 3 as a colorless liquid. Yield: 3.2 g (10.7 mmol; 45%). 1H-NMR in CDCl3 (δ, ppm): 5.05 (1H, q, J=5.0, 3.5 Hz, THP), 4.73 (1H, s, acetal), 3.92 (1H, m, THP), 3.69 (2H, m, CH2, acetal), 3.62 (2H, m, CH2, acetal), 3.50 (1H, m, THP), 1.82 (1H, m, THP), 1.71 (1H, m, THP), 1.58 (3H, s, CH3), 1.54 (3H, s, CH3), 1.52 (4H, m, THP), 1.25 (6H, t, J=7.0 Hz, CH3, acetal). 13C-NMR in CDCl3 (δ, ppm): 182.6, 101.1, 97.87, 96.10, 81.25, 70.57, 62.95, 62.64, 62.61, 31.47, 29.45, 28.85, 25.06, 19.92, 14.90 IR (neat, cm−1): 2978, 2937, 2872, 2214, 1687, 1074. HR ESIMS+ with acetonitrile as the mobile phase, (m/z): 299.1837 (M+, C16H26O5, 299.1853), 321.1660 (m/z) ([M+Na]+, C16H26O5Na, 321.1672). the stirring continued for 12 hours The aqueous layer was extracted with Et2O (3×50 mL) The organic solvent was separated with a separating funnel dried with anhydrous MgSO4 The solvent was removed under reduced pressure the resulting pale yellow oil was purified by radial chromatography (stationary phase silica gel, hexane/AcOEt 90:10)

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1.0 M solution of lithium hexamethyldisilazide in THF (310 mmol, 310 mL) was diluted with 20 mL of THF and cooled to -70° C. (internal temperature) with an acetone/dry ice bath under N2. A solution of 4'-methylacetophenone (150 mmol, 20.1 g, 20 mL) in 50 mL of tetrahydrofuran (THF) was added dropwise over a 15 min period, keeping the internal temperature below -60° C. After 1 h, the cooling bath was removed and the temperature was allowed to rise to -25° C. The reaction flask was immersed in an ice/acetone bath and a solution of ethyl diethoxyacetate (160 mmol, 28 g, 28.6 mL) in 20 mL of THF was added dropwise; during the addition, the internal temperature was kept below 0° C. The brown-red solution was stirred for 24 h and was re-cooled to 0° C. Aqueous HCl (3N, 618 mmol, 206 mL) was added carefully (temperature kept below 20° C.) to bring the pH to 3-4. The layers were separated and the aqueous layer was extracted with 200 mL of ether. The combined organic layers were washed twice with brine, dried over Na2SO4, and concentrated to give 40.3 g (100%) Cpd. 46 as an orange oil; 1H NMR (CDCl3, 300 MHz) 1.30 (t, 6H, J=7), 2.42 (s, 3H), 3.5-3.8 (complex, 4H), 4.90 (s, 1H), 6.58 (s, 1H), 7.28 (d, 2H, J=8), 7.74 (d, 2H, J=8), 15.8 (broad s, 1H) the internal temperature below -60° C the cooling bath was removed to rise to -25° C The reaction flask was immersed in an ice/acetone bath during the addition was kept below 0° C was re-cooled to 0° C The layers were separated the aqueous layer was extracted with 200 mL of ether The combined organic layers were washed twice with brine dried over Na2SO4 concentrated to give 40.3 g (100%) Cpd

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

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