cyclohexen-1-yloxy(trimethyl)silane

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 (R,R)-mono(2,6-dimethoxybenzoyl)tartaric acid (314 mg) in propionitrile (5 ml) was added 1M BH3 solution (1.0 ml) in tetrahydrofuran at 0° C. under N2. The reaction mixture was stirred for 1 hour at 0° C., and then the solution was cooled to -78° C. To this were added 1-(trimethylsilyl-oxy)cyclohexene (1.0 g) and 3-methoxybenzaldehyde (680 mg) successively. After stirring for 2 hours, the solution was poured into 1N-hydrochloric acid and the product was extracted with ether. The solvent was evaporated, and the residue was treated with 1N-hydrochloric acid-tetrahydrofuran solution (2 ml, 1:1). Usual chromatographic separation gave (2R)-2-(1-hydroxy-1-(3-methoxyphenyl)methyl]cyclohexanone (350 mg). the solution was cooled to -78° C After stirring for 2 hours the product was extracted with ether The solvent was evaporated the residue was treated with 1N-hydrochloric acid-tetrahydrofuran solution (2 ml, 1:1) Usual chromatographic separation

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

Procedure: 4.34 g (0.02 mol) of (2R,3R)-2-benzyloxybutane-1,3,4-triol were suspended in a mixture of 3.4 g (0.02 mmol) of 1-cyclohexenyloxytrimethylsilane and 40 ml of diethyl ether. Two drops of concentrated hydrochloric acid were added and the mixture was stirred at room temperature for 30 minutes. The mixture was then evaporated to give 5.65 g of β(R)-benzyloxy-1,4-dioxaspiro[4,5]decane-2(R)-ethanol in the form of a colourless viscous oil; MS: m/e 292 [M]+. The mixture was then evaporated

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

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

Procedure: 4.34 g (0.02 mol) of (2R,3R)-2-benzyloxybutane-1,3,4-triol were suspended in a mixture of 3.4 g (0.02 mmol) of 1-cyclohexenyloxytrimethylsilane and 40 ml of diethyl ether. Two drops of concentrated hydrochloric acid were added and the mixture was stirred at room temperature for 30 minutes. The mixture was then evaporated to give 5.65 g of β(R)-benzyloxy-1,4-dioxaspiro [4,5]decane-2 (R)-ethanol in the form of a colourless viscous oil; MS: m/e 292 [M]+. The mixture was then evaporated

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

Procedure: 4.34 g (0.02 mol) of (2R,3R)-2-benzyloxybutane-1,3,4-triol were suspended in a mixture of 3.4 g (0.02 mmol) of 1-cyclohexenyloxytrimethylsilane and 40 ml of diethyl ether. Two drops of concentrated hydrochloric acid were added and the mixture was stirred at room temperature for 30 minutes. The mixture was then evaporated to give 5.65 g of β(R)-benzyloxy-1,4-dioxaspiro [4,5]decane-2 (R)-ethanol in the form of a colourless viscous oil; MS: m/e 292 [M]+. The mixture was then evaporated

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of compound 6-benzyl-7-hydroxy-3-phenyl-(3S, 7aR)-perhydroimidazo[1,5-C][1,3]thiazol-5-one of formula (6) (0.326 parts, 1 mmol) in dichloromethane (10 parts) was added 1-trimethylsilyloxy-1-cyclohexene (0.340 parts. 2 mmol). Then the solution was cooled to 20° C., and Lewis acid for example BF3.Et2O (0.142 parts, 1 mmol) was added drop wise. The reaction mixture was stirred at 20° C. for 10 mints. and the reaction mixture was quenched with saturated ammonium chloride (10 parts). Then the organic layer was separated, concentrated and column purification with ethylacetate:pet.ether (15:85) as eluent provided compound 6-benzyl-7-(2-oxocyclohexyl)-3-phenyl-(3S, 7S, 7aR)-perhydroimidazo[1,5-C][1,3]-thiazol-5-one of formula (7d) (viscous liquid, 0.398 parts, 0.98 mmol) in98% yield. and the reaction mixture was quenched with saturated ammonium chloride (10 parts) Then the organic layer was separated concentrated column purification with ethylacetate

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

Procedure: A solution of 1-(trimethylsiloxy)cyclohexene (200 mg, 1.17 mmol) and benzyl 3-oxoazetidine-1-carboxylate (289 mg, 1.41 mmol), prepared using procedures similar to those described in Reference 3, in tetrahydrofuran (3.90 mL) was cooled to −78° C. for 10 minutes followed by the addition of titanium tetrachloride (0.13 mL, 1.17 mmol). The reaction mixture stirred for an additional 5 hours at −78° C. The mixture was quenched with aqueous sodium bicarbonate and the aqueous layer was extracted with ether (2×). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was purified on silica gel chromatography column (3:2 hexanes/ethyl acetate) to afford benzyl 3-hydroxy-3-(2-oxocyclohexyl)azetidine-1-carboxylate (328 mg, 37%). 1H NMR (CDCl3): 7.28-7.34 (m, 5H), 5.08 (s, 2H), 4.02 (d, 1H), 3.89 (d, 1H), 3.87 (s, 1H), 3.55 (s, 1H), 2.71 (q, 1H), 2.29-2.43 (m, 2H), 2.11 (s, 2H), 1.95 (s, 1H), 1.66 (d, 3H); MS (EI) for C17H21NO4: 303 (MH+). The mixture was quenched with aqueous sodium bicarbonate the aqueous layer was extracted with ether (2×) The organic layer was separated dried over anhydrous sodium sulfate filtered the filtrate was concentrated in vacuo The residue was purified on silica gel chromatography column (3:2 hexanes/ethyl acetate)

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

Procedure: A solution of 1-(trimethylsiloxy)cyclohexene (200 mg, 1.17 mmol) and benzyl 3-oxoazetidine-1-carboxylate (289 mg, 1.41 mmol), prepared using procedures similar to those described in Reference 3, in tetrahydrofuran (3.90 mL) was cooled to −78° C. for 10 minutes followed by the addition of titanium tetrachloride (0.13 mL, 1.17 mmol). The reaction mixture stirred for an additional 5 hours at −78° C. The mixture was quenched with aqueous sodium bicarbonate and the aqueous layer was extracted with ether (2×). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was purified on silica gel chromatography column (3:2 hexanes/ethyl acetate) to afford benzyl 3-hydroxy-3-(2-oxocyclohexyl)azetidine-1-carboxylate (328 mg, 37%). 1H NMR (CDCl3): 7.28-7.34 (m, 5H), 5.08 (s, 2H), 4.02 (d, 1H), 3.89 (d, 1H), 3.87 (s, 1H), 3.55 (s, 1H), 2.71 (q, 1H), 2.29-2.43 (m, 2H), 2.11 (s, 2H), 1.95 (s, 1H), 1.66 (d, 3H); MS (EI) for C17H21NO4: 303 (MH+). The mixture was quenched with aqueous sodium bicarbonate the aqueous layer was extracted with ether (2×) The organic layer was separated dried over anhydrous sodium sulfate filtered the filtrate was concentrated in vacuo The residue was purified on silica gel chromatography column (3:2 hexanes/ethyl acetate)

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

Procedure: Water (0.25 ml) was added to the silica gel supporting scandium produced in Example 1 (75 mg), and while stirring, benzaldehyde (0.125 mmol) and o-anisidine (0.125 mmol) and 1-cyclohexenyloxytrimethylsilane (0.25 mmol) were continuously added. The mixture was stirred at room temperature for 24 hours. The mixture was extracted four times by a decantation method using a mixture of ethyl acetate-hexane (1:1), the solvent was distilled off under reduced pressure, and then the residue was purified by silica gel thin layer chromatography, to obtain the target product, 2-(phenyl-N-(2-methoxyphenyl)aminomethyl)cyclohexanone at a syn/anti ratio of 53/47. Yield 92%. The mixture was stirred at room temperature for 24 hours The mixture was extracted four times by a decantation method a mixture of ethyl acetate-hexane (1:1) the solvent was distilled off under reduced pressure the residue was purified by silica gel thin layer chromatography

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

Procedure: 4.34 g (0.02 mol) of (2R,3R)-2-benzyloxybutane-1,3,4-triol were suspended in a mixture of 3.4 g (0.02 mmol) of 1-cyclohexenyloxytrimethylsilane and 40 ml of diethyl ether. Two drops of concentrated hydrochloric acid were added and the mixture was stirred at room temperature for 30 minutes. The mixture was then evaporated to give 5.65 g of β(R) -benzyloxy-1,4-dioxaspiro[4,5]decane-2(R)-ethanol in the form of a colourless viscous oil; MS: m/e 292 [M]+. The mixture was then evaporated

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

Procedure: To a solution of (R,R)-mono(2,6-dimethoxybenzoyl)tartaric acid (314 mg) in propionitrile (5 ml) was added 1M BH3 solution (1.0 ml) in tetrahydrofuran at 0° C. under N2. The reaction mixture was stirred for 1 hour at 0° C., and then the solution was cooled to -78° C. To this were added 1-(trimethylsilyl-oxy)cyclohexene (1.0 g) and 3-methoxybenzaldehyde (680 mg) successively. After stirring for 2 hours, the solution was poured into 1N-hydrochloric acid and the product was extracted with ether. The solvent was evaporated, and the residue was treated with 1N-hydrochloric acid-tetrahydrofuran solution (2 ml, 1:1). Usual chromatographic separation gave (2R)-2-(1-hydroxy-1-(3-methoxyphenyl)methyl]cyclohexanone (350 mg). the solution was cooled to -78° C After stirring for 2 hours the product was extracted with ether The solvent was evaporated the residue was treated with 1N-hydrochloric acid-tetrahydrofuran solution (2 ml, 1:1) Usual chromatographic separation