Reaction SMILES: [C:1]([O:4][C@H:5]1[C@@H:8]([CH:9]([CH3:11])[CH3:10])[N:7](CC2C=CC(OC)=CC=2)[C:6]1=[O:21])(=[O:3])[CH3:2]>O.C(#N)C>[C:1]([O:4][C@H:5]1[C@@H:8]([CH:9]([CH3:10])[CH3:11])[NH:7][C:6]1=[O:21])(=[O:3])[CH3:2]
Reactant: COc1ccc(CN2C(=O)[C@@H](OC(C)=O)[C@H]2C(C)C)cc1
Solvent: O
Solvent: CC#N
Product: CC(=O)O[C@@H]1C(=O)N[C@@H]1C(C)C
Yield: 95.7 %

Procedure:
Isobutyraldehyde (4.62 mL, 1.25 equiv) was added to a strirred suspension of p-anisidine (5.00 gm, 40.7 mmole) and anhydrous Na2SO4 (25 gm) in anhydrous DCM (80 mL) at RT. After 1 hr, this was filtered and the solid was washed with additional anhydrous DCM. The solvent was removed from the filtrate and the residue was dissolved in anhydrous DCM (200 mL) and placed under a nitrogen atmosphere. Triethylamine (13.1 mL, 2.3 equiv) was added and the reaction was cooled to −78° C. Acetoxyacetyl chloride (5.00 mL 1.15 equiv) was added dropwise and the reaction was allowed to warm to RT. After 20 hr, this was washed with 0.5 M HCl (twice), sat. aqueous NaHCO3 solution, brine and dried (Na2SO4), the solvent was removed and the residue was chromatographed on a silica gel column (gradient elution with 20 to 30% EtOAc in hexane) to afford (±)-cis-3-acetoxy-4-isopropyl-1-p-methoxybenzyl-azetidin-2-one as a solid (7,15 gm, 63%): 1H NMR (CDCl3) 80.99 (d, 3H, J=7.0 Hz), 1.02 (d, 3H, J=7.0 Hz), 2.20 (s, 3H), 3.82 (s, 3H), 4.24 (t, 1H, J=5.6 Hz), 6.06 (d, 1H, J=5.3 Hz), 6.88-7.38 (m, 4H). A solution of ceric ammonium nitrate (51.3 gm 3.6 equiv) in 750 mL of water was added to a well stirred solution of the azetidinone (7.20 gm, 26.0 mmole) in acetonitrile (500 mL) in an ice bath over 1 hr. The reaction was then extracted with EtOAc (twice) and the combined organic extracts were washed with sat. aqueous NaHCO3 solution (twice), 20% aqueous NaHSO3 solution, sat. aqueous NaHCO3 solution and brine. After being dried (Na2SO4) the solvents were removed to leave 4.26 gm of crude (+)-cis-3-acetoxy-4-iso-propyl-azetidin-2-one: 1H NMR (CDCl3) δ 0.86 (d, 3H, J=6.6 Hz), 0.99 (d, 3H, J=6.6 Hz), 1.89 (m, 1H), 2.17 (s, 3H), 3.52 (dd, 1H, J=4.8, 9.0 Hz), 5.96 (dd, 1H, J=2.5, 4.6 Hz), 6.38 (br s, 1H), LRMS (negative ESI) 170 [(M−H)−]. A suspension of this material (4.26 gm, 24.9 mmole) and K2CO3 (102 mg, 0.03 equiv) in MeOH (40 mL) was left stirring at RT for 1.5 hr. Amberlite IR-20 was then added to neutralize the reaction. This was filtered and the solvent was removed from the filtrate to leave crude (+)-cis-3-hydroxy-4-iso-propyl-azetidin-2-one. This material was dissolved in dry DMF (40 mL) and imidazole (3.39 gm, 2 equiv) and triethylsilyl chloride (4.19 mL, 1 equiv) were added. After 10 min, the reaction was partitioned between water and a mixture of EtOAc and hexane (1:1). The organic phase was washed with water (twice), brine and then dried (Na2SO4). The solvents were removed and the residue was chromatographed on a silica gel column (gradient elution with 25 to 35% EtOAc in hexane) to give (±)-cis-4-isopropyl-3-triethylsilyloxy-azetidin-2-one (4.63 gm, 77%): 1H NMR (CDCl3) δ 0.65-1.03 (m, 21H), 1.93 (m, 1H), 3.29 (dd, 1H, J=4.8, 9.1 Hz), 4.87 (dd, 1H, J=2.8, 4.7 Hz), 6.05 (br s, 1H). A solution of this azetidinone (1.05 gm, 4.32 mmole), diisopropylethyl amine (0.90 mL, 1.2 equiv), di-tert-butyl dicarbonate (1.04 gm, 1.1 equiv) and p-dimethylamino pyridine (106 mg, 0.2 equiv) in dry DCM (10 mL) was left stirring at RT for 30 min. The reaction was diluted with DCM, washed with brine and dried (Na2SO4). Removal of the solvent followed by silica gel column chromatography (gradient elution with 10 to 20% EtOAc in hexane) afforded 1.31 gm (88%) of the title compound as an oil: 1H NMR δ (CDCl3) 0.66-1.07 (m, 21H), 1.53 (s, 9H), 2.15 (m, 1H), 3.87 (t, 1H, J=6.4 Hz), 4.88 (d, 1H, J=6.1 Hz); LRMS (ESI) 344 [(M+H)]+.