benzyl acetate

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: A stirred 2-liter autoclave is charged with toluene (400g), cobaltous 2-ethyl hexanoate (2g), acetic anhydride (50g) and potassium cyanide (25g) in that order in the confines of a well ventilated hood. The autoclave is sealed, flushed with N2 and heated to 150° whereupon the N2 pressure of 176 psig is increased to 220 psig with oxygen. The oxygen pressure is maintained at 45 psig during the reaction and at completion of the reaction the product is isolated by distillation. At 1.5% conversion of the toluene there is a 25% yield of benzyl acetate and 72% yield of 2-cyanobenzyl acetate based on the toluene converted. The autoclave is sealed flushed with N2 heated to 150° whereupon the N2 pressure of 176 psig is increased to 220 psig with oxygen The oxygen pressure is maintained at 45 psig during the reaction and at completion of the reaction the product is isolated by distillation

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

Procedure: To a flame dried, 50 ml, 3-neck flask fitted with a N2 inlet, magnetic stirrer, addition funnel, and serum cap are added anhydrous tetrahydrofuran (THF) (10.5 ml) and diisopropyl amine (0.579 ml, 4.13 mmol). The solution is cooled in an ice-methanol bath under N2 and treated with 2.4N n-butyl lithium in hexane (1.72 ml). After being stirred at -10° for 15 mins, the solution is cooled to -78° and treated dropwise over 9 mins with a solution of benzyl acetate (0.620 g, 4.13 mmol) in anhydrous THF (3.5 ml). After stirring 15 more mins at -78° C. the reaction mixture is treated dropwise over 13 mins with a solution of N-(t-butyldimethylsilyl)-4-(2-oxoethyl)-azetidin-2-one (0.894 g, 3.93 mmol) in anhydrous THF (6 ml). The reaction mixture is stirred at -78° an additional 15 mins and then quenched with 2.5N HCl (6 ml). EtOAc (100 ml) is added and the oragnic phase is separated, washed with H2O (2×20 ml), 5% NaHCO3 (20 ml) and brine, dried with MgSO4, and filtered. The filtrate is evaporated i.v. and the residue stripped with φH to yield N-(t-butyldimethylsilyl)-4-(3-benzyloxycarbonyl-2-hydroxypropyl)-azetidin-2-one (1.432 g) as an oil: ir (neat) 2.87, 5.73, 5.79, 7.57, 7.96, 8.39, 11.92, and 12.16 cm-1 ; mass spectrum m/e 362, 320, 278, 170 and 128. To a flame dried 50 ml, 3-neck flask fitted with a N2 inlet, magnetic stirrer, addition funnel serum cap The solution is cooled in an ice-methanol bath under N2 the solution is cooled to -78° After stirring 15 more mins at -78° C. the reaction mixture The reaction mixture is stirred at -78° an additional 15 mins quenched with 2.5N HCl (6 ml) EtOAc (100 ml) is added the oragnic phase is separated washed with H2O (2×20 ml), 5% NaHCO3 (20 ml) and brine dried with MgSO4 filtered The filtrate is evaporated i.v

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

Procedure: A solution of 21.9 mL (156 mmol) of diisopropylamine in dry THF (100 mL) was cooled to -40° C. under nitrogen, treated dropwise with 125 mL of 1.2M n-BuLi (150 mmol), and stirred for 30 minutes. To this solution was added a solution of 22.5 g (150 mmol) of benzyl acetate in dry THF (70 mL). The mixture was stirred at -40° C. for 45 minutes and then treated with a solution of 16.2 g (50 mmol) of [4-(4-methyl-3-oxo-pentyl)-phenyl]-carbamic acid benzyl ester (prepared in Example HHHHH) at a rapid, dropwise rate. When addition was complete, the reaction mixture was stirred at -40° C. for 30 minutes. Acetic acid (50 mL) was added, and the mixture was warmed to room temperature. EtOAc and H2O were added. The organic layer was separated, washed with brine, and dried (MgSO4). Concentration gave a residue which was chromatographed on silica gel, eluting with EtOAc:hexane (40:60), to give the title compound. 1H NMR (CDCl3) δ 0.88-0.91 (t, 6 H), 1.65-1.75 (m, 2 H), 1.85-1.89 (m, 1 H), 2.46-2.61 (m, 4 H), 3.52 (s, 1 H), 5.11 (s, 2 H), 5.16 (s, 2 H), 6.55 (br s, 1 H), 7.02 (d, 2 H), 7.24-7.38 (m, 12 H). The mixture was stirred at -40° C. for 45 minutes When addition the reaction mixture was stirred at -40° C. for 30 minutes The organic layer was separated washed with brine dried (MgSO4) Concentration gave a residue which was chromatographed on silica gel eluting with EtOAc:hexane (40:60)

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

Procedure: n-Butyllithium (1.81 mmol) is added by syringe to a solution of diisopropylamine (1.81 mmol) in 9 ml of freshly distilled tetrahydrofuran at -78° C. The resulting solution is stirred for 15 min at -78° C. Benzyl acetate (1.81 mmol) is then added dropwise by syringe and the resulting solution is stirred at -78° C. for 20 min. A solution of (3S, 4R)-1-(t-butyldimethylsilyl)-3[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-(2-oxoethyl)azetidin-2-one (1.64 mmol) in 3 ml of anhydrous tetrahydrofuran is added slowly by syringe. The reaction mixture is stirred at -78° C. an additional 15 min and then quenched by addition of saturated aqueous ammonium chloride solution. Ethyl acetate (50 ml) is added and the organic phase is separated, washed with water (2×10 ml) and brine and dried over magnesium sulfate. Removal of solvents in vacuo gives a white solid which is chromatographed on a short silica gel column (40% ether in petroleum ether) to yield (3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-(3-benzyloxycarbonyl-2-hydroxypropyl)-azetidin-2-one, n.m.r. (CDCl3) δ7.32(s,5), δ5,1(s,2), δ4.0(m,3), δ2,4-3,8(m,4), δ2.0(m,2), δ1.25(overlapping d,3), δ0.95(s,9), δ0.9(s,9), δ0.3(s,6), δ0.18(s,6). the resulting solution is stirred at -78° C. for 20 min The reaction mixture is stirred at -78° C. an additional 15 min quenched by addition of saturated aqueous ammonium chloride solution Ethyl acetate (50 ml) is added the organic phase is separated washed with water (2×10 ml) and brine dried over magnesium sulfate Removal of solvents in vacuo gives a white solid which is chromatographed on a short silica gel column (40% ether in petroleum ether)

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

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