Reaction SMILES: C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7][CH2:6]1)=O.[BH4-].[Li+].C([BH-](CC)CC)C.[Li+]>CCOCC.C1COCC1>[CH3:18][C:15]([O:14][C:12]([NH:11][CH:8]1[CH2:7][CH2:6][CH:5]([CH2:3][OH:2])[CH2:10][CH2:9]1)=[O:13])([CH3:16])[CH3:17]
Reactant: COC(=O)[C@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
Agent: CC[BH-](CC)CC
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(C)(C)OC(=O)NC1CCC(CO)CC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 99.8 %

Procedure:
Step 1. To a stirred solution of trans-4-aminocyclohexanecarboxylic acid methyl ester hydrochloride (1.0 g, 5.17 mmol) and triethylamine (2 ml) in CH2Cl2 (30 ml) was added Boc2O (1.20 g, 5.50 mmol). The resulting mixture was stirred at rt overnight. After removal of the solvent, the residue was washed with water (30 ml) and dried in vacuo to give trans-4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid methyl ester (1.10 g, 83%) as a colorless solid. mp 80-81° C.; 1H NMR (500 MHz, CDCl3) δ 1.05-1.16 (m, 2H), 1.46-1.58 (m, 2H), 1.44 (s, 9H), 1.97-2.11 (m, 4H), 2.18-2.27 (m, 1H), 3.41 (brs, 1H), 3.66 (s, 3H), 4.38 (brs, 1H); 13C NMR (125.7 MHz, CDCl3) δ 27.79, 28.39, 32.53, 42.35, 48.95, 51.63, 79.22, 155.13, 175.86. Step 2. To a solution of trans-4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid methyl ester (1.00 g, 3.89 mmol) in ether (40 ml) and THF (8 ml) was added dropwise 2 M lithium borohydride in THF (1.95 ml, 3.89 mmol) followed by 1 M lithium triethylborohydride in THF (0.40 ml, 0.39 mmol). The resulting mixture was stirred at rt for 24 h and then diluted with ether (30 ml). The mixture was washed with 2 M aq. NaOH (2×5 ml), water (2×5 ml) and brine (5 ml), dried over MgSO4, filtered, and concentrated to afford tert-butyl trans-(4-hydroxymethyl)cyclohexylcarbamate as a colorless solid (0.89 g, 99%). mp 124-125° C. 1H NMR (500 MHz, CDCl3) δ 1.00-1.15 (m, 2H), 1.44 (s, 9H), 1.50-1.64 (m, 2H), 1.79-1.86 (m, 2H), 2.02-2.08 (m, 2H), 3.39 (brs, 1H), 3.46 (d, J=6.0 Hz, 2H), 4.39 (brs, 1H); 13C NMR (125.7 MHz, CDCl3) δ 28.18, 28.40, 32.89, 39.58, 49.84, 68.06, 79.07, 155.20. Step 3. Diisopropyl azodicarboxylate (0.69 ml, 3.24 mmol) was added dropwise to a mixture of OZ288 (1.00 g, 2.80 mmol), tert-butyl trans-(4-hydroxymethyl)cyclohexylcarbamate (0.64 g, 2.80 mmol), and triphenylphosphine (0.85 g, 3.24 mmol) in THF (50 ml) at 0° C. under Ar. The resulting mixture was stirred at rt for 24 h. After removal of the solvent, the crude product was purified by crystallization from EtOH to afford the desired BOC derivative (0.52 g, 33%) as a colorless solid. mp 157-158° C.; 1H NMR (500 MHz, CDCl3) δ 1.07-1.20 (m, 2H), 1.44 (s, 9H), 1.64-2.10 (m, 29H), 2.44-2.54 (m, 1H), 3.42 (brs, 1H), 3.72 (d, J=6.0 Hz, 2H), 4.39 (brs, 1H), 6.80 (d, J=9.0 Hz, 2H), 7.10 (d, J=9.0 Hz, 2H); 13C NMR (125.7 MHz, CDCl3) δ 26.46, 26.87, 28.42, 28.54, 31.65, 32.90, 34.74, 34.79, 36.38, 36.79, 36.93, 42.04, 49.79, 72.78, 79.11, 108.45, 111.36, 114.26, 127.58, 138.22, 155.20, 157.43. Step 4. A mixture of the BOC derivative (0.40 g, 0.71 mmol) and MsOH (1.5 M in THF, 12 ml, 180 mol) was stirred at rt for 4 h. The resulting precipitate was filtered off, washed with ether (30 ml), and dried in vacuo to afford trioxolane OZ545 (0.32 g, 81%) as a colorless solid. mp 168-169° C.; 1H NMR (500 MHz, CDCl3) δ 1.11-1.27 (m, 2H), 1.45-1.59 (m, 2H), 1.64-2.25 (m, 27H), 2.44-2.54 (m, 1H), 2.80 (s, 3H), 3.04-3.16 (m, 1H), 3.73 (d, J=6.0 Hz, 2H), 6.79 (d, J=9.0 Hz, 2H), 7.10 (d, J=9.0 Hz, 2H), 7.61 (brs, 3H); 13C NMR (125.7 MHz, CDCl3) δ 26.48, 26.88, 27.65, 30.20, 31.65, 34.74, 34.80, 36.40, 36.80, 42.04, 72.24, 108.44, 111.36, 114.29, 127.62, 138.39, 157.30.