4-Trimethylsilyl-3-butyn-2-ol

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

Procedure: To a solution of ii (10.0 g, 0.14 mol) in ether (200 mL) was added ethylmagnesium bromide (105 mL, 3 M in THF, 0.32 mol) dropwise at 0° C. The resulting solution was refluxed for 1.5 h. After the reaction solution was cooled to 0° C., trimethylsilyl chloride (40 mL, 0.32 mol) was added. The solution was warmed to room temperature and stirred overnight. Hydrochloric acid (100 mL, 10%) was added at 0° C. After 20 min, the two layers were separated. The aqueous layer was extracted with ether (2×50 mL). The combined organic solutions were dried over anhydrous magnesium sulfate, filtered and concentrated. Distillation of the residue gave 19.9 g (98%) ii-a as a colorless liquid: bp 80.5°-83.5° C. /17.5 mm Hg; IR (neat) 3337, 2175, 1452, 1251, 1119, 1048, and 946 cm-1 ; 1NMR (CDCl3, 300 MHz) δ4.42 (q, J=6.6 Hz, 1H, CHOH), 3.12 (br s, 1H, OH), 1,16 (d, J=6.6 Hz, 3H, CHCH3), and 0.08 (s, 9H, SiCH3); 13C NMR (CDCl3, 75.5 MHz) δ108.12, 88.19, 58.61, 24. 05, and 0.01. The resulting solution was refluxed for 1.5 h The solution was warmed to room temperature After 20 min the two layers were separated The aqueous layer was extracted with ether (2×50 mL) The combined organic solutions were dried over anhydrous magnesium sulfate filtered concentrated Distillation of the residue gave 19.9 g (98%) ii-a as a colorless liquid

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

Procedure: A solution of 94.15 parts by weight of 4-(trimethylsilyl)-3-butyn-2-ol (II) in 940 parts by volume of benzene and 4.7 parts by volume of quinoline is hydrogenated at a constant pressure of 2 p.s.i. in the presence of 9.4 parts by weight of 5% palladium on barium sulfate until one equivalent of hydrogen is consumed. The catalyst is removed and the solution is washed twice with 100 parts per volume of 5% aqueous hydrochloric acid and then with water. After drying over sodium sulfate, the solvent is removed and the residue is distilled at 33°-39° C./0.3 mm to give cis-4-(trimethylsilyl)-3-buten-2-ol (III) which has the following structural formula: ##STR9## The catalyst is removed the solution is washed twice with 100 parts per volume of 5% aqueous hydrochloric acid After drying over sodium sulfate the solvent is removed the residue is distilled at 33°-39° C./0.3 mm

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

Procedure: A solution of 107.1 parts by weight of 3-butyne-2-ol (I) in 1000 parts by volume of dry ethyl ether is chilled to -50° C. (internal temperature) and 1390 parts by volume of 2.17 M n-butyl lithium in hexane is added over a 2 hour period. The internal temperature is allowed to reach 10° C. during the latter part of the addition to facilitate stirring. The mixture is then cooled again to -30° C. (internal) and 400 parts by volume of chlorotrimethylsilane in 200 parts by volume of ethyl ether is added over a 15 minute period. The mixture is allowed to warm slowly to room temperature overnight. After a brief period of reflux the mixture is again cooled to 25° C. and 100 parts by volume of water is added causing the internal temperature to rise to 37° C. After stirring for 1 hour, more water is added. The organic layer is separated and washed with 5% aqueous hydrochloric acid and water. The solution is dried over sodium sulfate, then concentrated to approximately 400 parts by volume. After adding 500 parts per volume of methanol and 200 parts per volume of 5% hydrochloric acid the solution is stirred at room temperature for one hour then diluted with 1000 parts per volume of water and extracted with ether. The ether extract is washed with water, dried over sodium sulfate and concentrated to afford 4-(trimethylsilyl)-3-butyn-2-ol (II) which distills at 49°-50° C./0.25 mm and has the following structural formula ##STR8## is added over a 2 hour period to reach 10° C. during the latter part of the addition is added over a 15 minute period After a brief period of reflux the mixture is again cooled to 25° C. to rise to 37° C After stirring for 1 hour The organic layer is separated washed with 5% aqueous hydrochloric acid and water The solution is dried over sodium sulfate concentrated to approximately 400 parts by volume After adding 500 parts per volume of methanol and 200 parts per volume of 5% hydrochloric acid the solution is stirred at room temperature for one hour then diluted with 1000 parts per volume of water extracted with ether The ether extract is washed with water dried over sodium sulfate concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ii (10.0 g, 0.14 mol) in ether (200 mL) was added ethylmagnesium bromide (105 mL, 3M in THF, 0.32 mol) dropwise at 0° C. The resulting solution was refluxed for 1.5 h. After the reaction solution was cooled to 0° C., trimethylsilyl chloride (40 mL, 0.32 mol) was added. The solution was warmed to room temperature and stirred overnight. Hydrochloric acid (100 mL, 10%) was added at 0° C. After 20 min, the two layers were separated. The aqueous layer was extracted with ether (2×50 mL). The combined organic solutions were dried over anhydrous magnesium sulfate, filtered and concentrated. Distillation of the residue gave 19.9 g (98%) ii-a as a colorless liquid: bp 80.5°-83.5° C./17.5 mm Hg; IR (neat) 3337, 2175, 1452, 1251, 1119, 1048, and 946 cm-1 ; 1H NMR (CDCl3, 300 MHz) δ 4.42 (q, J=6.6 Hz, 1 H, CHOH), 3.12 (br S, 1 H, OH), 1,16 (d, J=6.6 Hz, 3 H, CHCH3), and 0.08 (s, 9 H, SiCH3); 13C NMR (CDCl3, 75.5 MHz) δ 108.12, 88.19, 58.61, 24. 05, and 0.01. The resulting solution was refluxed for 1.5 h The solution was warmed to room temperature After 20 min the two layers were separated The aqueous layer was extracted with ether (2×50 mL) The combined organic solutions were dried over anhydrous magnesium sulfate filtered concentrated Distillation of the residue gave 19.9 g (98%) ii-a as a colorless liquid

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

Procedure: Referring to Flowchart II, 3-butyn-2-ol (formula 21) is treated in step H with sodium hydride in ether at -20° C. and then with 2.0 n-butyllithium in hexane, followed by chlorotrimethylsilane, to produce (+)-4-trimethylsilyl-3-butyn-2-ol (formula 22), which is then reacted in step I with lithium aluminum hydride in ether at reflux for several hours, basified and distilled, to produce (±)-trans-4-(trimethylsilyl)-3-buten-2-ol (formula 23). The reaction in step J of (23) in ether with a mixture of sodium dichromate hydrate and sulfuric acid at <5° C. or below produces trans-4-(trimethylsilyl)-3-buten-2-one (formula 24), which upon distillation with selected solvents gives trans-4-(trimethylsilyl)-2-acetoxy-1,3-butadiene (formula 25).

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ii (10.0 g, 0.14 mol) in ether (200 mL) was added ethylmagnesium bromide (105 mL, 3 M in THF, 0.32 mol) dropwise at 0° C. The resulting solution was refluxed for 1.5 h. After the reaction solution was cooled to 0° C., trimethylsilyl chloride (40 mL, 0.32 mol) was added. The solution was warmed to room temperature and stirred overnight. Hydrochloric acid (100 mL, 10%) was added at 0° C. After 20 min, the two layers were separated. The aqueous layer was extracted with ether (2×50 mL). The combined organic solutions were dried over anhydrous magnesium sulfate, filtered and concentrated. Distillation of the residue gave 19.9 g (98%) ii-a as a colorless liquid: bp 80.5°-83.5° C. /17.5 mm Hg; IR (neat) 3337, 2175, 1452, 1251, 1119, 1048, and 946 cm-1 ; 1NMR (CDCl3, 300 MHz) δ4.42 (q, J=6.6 Hz, 1H, CHOH), 3.12 (br s, 1H, OH), 1,16 (d, J=6.6 Hz, 3H, CHCH3), and 0.08 (s, 9H, SiCH3); 13C NMR (CDCl3, 75.5 MHz) δ108.12, 88.19, 58.61, 24. 05, and 0.01. The resulting solution was refluxed for 1.5 h The solution was warmed to room temperature After 20 min the two layers were separated The aqueous layer was extracted with ether (2×50 mL) The combined organic solutions were dried over anhydrous magnesium sulfate filtered concentrated Distillation of the residue gave 19.9 g (98%) ii-a as a colorless liquid

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

Procedure: A solution of 94.15 parts by weight of 4-(trimethylsilyl)-3-butyn-2-ol (II) in 940 parts by volume of benzene and 4.7 parts by volume of quinoline is hydrogenated at a constant pressure of 2 p.s.i. in the presence of 9.4 parts by weight of 5% palladium on barium sulfate until one equivalent of hydrogen is consumed. The catalyst is removed and the solution is washed twice with 100 parts per volume of 5% aqueous hydrochloric acid and then with water. After drying over sodium sulfate, the solvent is removed and the residue is distilled at 33°-39° C./0.3 mm to give cis-4-(trimethylsilyl)-3-buten-2-ol (III) which has the following structural formula: ##STR9## The catalyst is removed the solution is washed twice with 100 parts per volume of 5% aqueous hydrochloric acid After drying over sodium sulfate the solvent is removed the residue is distilled at 33°-39° C./0.3 mm