Reaction SMILES: [CH2:1]([O:8][C:9](=[O:32])[NH:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([NH:17][CH:18]([CH3:20])[CH3:19])[CH2:13][C@H:12]1[CH2:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[BH3-][C:36]#N.[Na+]>CO.O>[CH2:1]([O:8][C:9](=[O:32])[NH:10][C@H:11]1[CH2:16][CH2:15][C@@H:14]([N:17]([CH:18]([CH3:20])[CH3:19])[CH3:36])[CH2:13][C@H:12]1[CH2:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [BH3-]C#N
Reactant: CC(C)N[C@H]1CC[C@H](NC(=O)OCc2ccccc2)[C@H](CS(=O)(=O)c2ccc(Br)cc2)C1
Agent: C=O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC(C)N(C)[C@@H]1CC[C@H](NC(=O)OCc2ccccc2)[C@H](CS(=O)(=O)c2ccc(Br)cc2)C1
Reaction time: 0.17 h
Yield: 616.8 %

Procedure:
1,4-Cyclohexanedione mono-ethylene ketal (25 g) was dissolved in THF and cooled to −78° C. 1.0 M Lithium bis(trimethylsily)amide (160 mL) in THF was added dropwise. After 30 min, ethyl cyanoformate (15.9 mL) was added dropwise. After 60 min, the solution was poured into EtOAc and water containing ice. The organic layer was washed with water and brine before it was dried and concentrated. This crude was filtered through a plug of silica to give the 8-oxo-1,4-dioxa-spiro[4.5]decane-7-carboxylic acid ethyl ester (32.4 g). MS found: (M+H)+=228.9. (3b) The above derivative (3a) (36.5 g) was dissolved in toluene (500 ml) prior to the addition of (S)-methylbenzyl amine (23 ml) and ytterbium (III) triflate (0.37 g). This miture was stirred at reflux for 3 h. After cooling to rt overnight, the solvent was removed to a golden oil. This oil was dissolved in acetonitrile (420 ml) prior to the addition of acetic acid (100 ml) and NaBH(OAc)3 (67.8 g). The mixture was stirred for 5 days at rt. The solvent was removed before being redissolved in CH2Cl2. After cooling in an ice bath, 1N NaOH was added (pH=8). The organic layer was washed with brine, dried, filtered, and concentrated. Flash chromatography of the resulting residue gave 8(S)-(1(S)-phenyl-ethylamino)-1,4-dioxa-spiro[4.5]decane-7(R)-carboxylic acid ethyl ester (26.2 g): 1H NMR (CDCl3, δ ppm, 300 mHz) 1.31 (m, 6H), 1.46 (m, 1H), 1.6-1.84 (m, 4H), 2.1 (t, 1H), 2.85 (m, 1H), 3.16 (m, 1H), 3.76 (m, 1H), 3.93 (m, 4H), 4.19 (q, 2H), 7.2-7.4 (m, 5H). (3) The above derivative (3b) (16.3 g) was dissolved in Et2O (160 ml) and cooled to 0° C. 1.0 M lithium aluminum hydride in THF (117.3 mL) was added dropwise. After the addition, the solution was stirred for 2 h at 0° C. The reaction was quenched with water (4.4 mL) and then 1N NaOH (17.6 ml). The solids were filtered off through a pad of celite. The filtrate was concentrated to an oil. This material was dissolved in MeOH (20 ml) prior to the addition of 20% Pd(OH)2 (3 g). This solution was placed on a Parr aparatus at 50 psi. The solution was mixed overnight. The palladium was filtered off and the solution was concentrated. The resulting oil was dissolved in THF (160 ml) and water (20 ml) prior to the addition of triethylamine (8.8 ml). After cooling to 0° C., dibenzyl dicarbonate (18.2 g) was added. The solution was warmed to rt and was stirred overnight. Ethyl acetate was added along with brine. The organic layer was washed with brine, dried, filtered, and concentrated. Flash chromatography of the resulting residue gave (7R,8S)-(7-hydroxymethyl-1,4-dioxa-spiro[4.5]dec-8-yl)-carbamic acid benzyl ester (9.8 g). MS found: (M+H)+=322.2. (3d) A portion (100 mg) of the above derivative (3c) was dissolved in THF (10 ml) prior to the addition of tri-n-butylphosphine (0.86 ml). 4-Bromophenyl disulfide (233 mg) was added and the solution was stirred in a 75° C. oil bath. After 5 h, the reaction was cooled to rt and flash chromatography gave (7R,8S)-[7-(4-bromo-phenylsulfanylmethyl)-1,4-dioxa-spiro [4.5] dec-8-yl]-carbamic acid benzyl ester (137 mg). 1H NMR (CDCl3, δ ppm, 300 mHz) 1.39 (t, 1H), 1.5-1.9 (m, 9H), 2.05 (m, 1H), 2.73 (m, 1H), 3.0 (dd, 1H), 3.93 (m, 4H), 4.08 (m, 1H), 4.9 (br d, 1H), 5.1 (s, 2H), 7.17 (d, 2H), 7.36 (m, 7H). (3e) A portion (2.5 g) of the above derivative (3d) was dissolved in CH2Cl2 (100 ml) and cooled to 0° C. prior to the addition 65% M—CPBA (3.1 g). After 2 h, the solution was washed with saturated NaHCO3 solution, brine solution, dried, filtered, and concentrated. Flash chromatography of the resulting residue gave (7R, 8S)-[7-(4-bromo-benzenesulfonylmethyl) -1,4-dioxa-spiro[4.5]dec-8-yl]-carbamic acid benzyl ester (2.59 g). MS found: (M+H)+=525. 9. (3f) The above derivative (3e) (2.6 g) was dissolved in CH3CN (25 ml) prior to the addition of 1N HCl (25 ml). The resulting solution was heated in an oil bath at 60° C. for overnight. After cooling, the solution was concentrated. EtOAc and 10% NaHCO3 were added. The organic layer was washed with brine, dried, filtered, and concentrated to give crude (7R, 8S) [2-(4-bromo-benzenesulfonylmethyl)-4-oxo-cyclohexyl]-carbamic acid benzyl ester (2.4 g). 1H NMR (CDCl3, δ ppm, 300 mHz) 1.96 (m, 2H), 2.40 (m, 2H), 2.75-2.96 (m, 4H), 3.30 (m, 1H), 4.20 (m, 1H), 5.11 (m, 3H), 7.40 (m, 5H) 7.75 (m, 4H). (3g) The above crude derivative (3f) (2.4 g) was dissolved in Ti(OiPr)4 (15 mL) prior to the addition of isopropylamine (2.1 ml). After 1.0 h, the reaction was cooled to 0° C. and MeOH (100 ml) was added slowly followed by NaBH4 (567 mg). After 1 h at 0° C., the reaction was quenched by the addition of 1N NaOH and filtered through celite. The filtrate was concentrated to a mixture of diastereomers. Flash chromatography of the resulting mixture gave two diastereomers [(1S, 2R, 4R)-2-(4-bromo-benzenesulfonylmethyl)-4-isopropylamino-cyclohexyl]-carbamic acid benzyl ester (3ga) (1.96 g), MS found: (M +H)+=523.3; and [(1S, 2R, 4S)-2-(4-bromo-benzenesulfonylmethyl)-4-isopropylamino-cyclohexyl]-carbamic acid benzyl ester (3gb) (300 mg). MS found: (M+H)+=523.3. (3h) The above derivative (3ga) (1.96 g) was dissolved in MeOH (15 mL) prior to the addition of 37% formaldehyde in water (1.41 ml). After 10 min, NaBH3CN (708 mg) was added. After 2 h, the reaction was concentrated. EtOAc was added and the organic layer was washed with H2O, brine, dried, filtered, and concentrated to give [(1S, 2R, 4R)-2-(4-Bromo-benzenesulfonylmethyl)-4-(isopropyl-methyl-amino)-cyclohexyl]-carbamic acid benzyl ester (1.9 g). MS found: (M+H)+=539.3 (3i) A portion (940 mg) of the above derivative (3h) was dissolved in 30 wt. % hydrogen bromide solution in acetic acid (6.9 ml). The resulting solution was stirred for 1 hr and then cooled to 0° C. Ether was added and solid was formed. The top liquid was decanted off. This process was repeated several times to give HBr salt (1S, 2R, 4R)-2-(4-bromo-benzenesulfonylmethyl)-N4-isopropyl-N4-methyl-cyclohexane-1,4-diamine (1.0 g). MS found: (M+2H)+=405.2 (3j) A portion of the above derivative (3i) (44 mg) was dissolved in DMF (2 ml) prior to the addition of 4-methylmorpholine (42 μl) and example (1d) (21.4 mg). After cooling to 0° C., BOP (52 mg) was added. The resulting mixture was warmed to rt and stirred overnight. The reaction was concentrated. Water was added and the solution was extracted with EtOAc. The organic layer was washed with NaHCO3 solution (aq), dried (MgSO4), filtered, and concentrated. Reverse phase HPLC purification (gradient elution, water/acetonitrile/TFA) of the resulting residue provided the title compound (25 mg).