Reaction SMILES: [CH:1]1([CH2:7][C@H:8]([NH:15][C:16]([C:18]2[O:19][C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=3)=[CH:21][CH:22]=2)=[O:17])[C:9](=[O:14])[NH:10][CH2:11][CH2:12]O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[F:55][CH:56]([F:65])[O:57][C:58]1[CH:64]=[CH:63][C:61]([NH2:62])=[CH:60][CH:59]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>C(Cl)Cl.CCOC(C)=O.CO>[CH:1]1([CH2:7][C@H:8]([NH:15][C:16]([C:18]2[O:19][C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:30])[F:31])[CH:24]=3)=[CH:21][CH:22]=2)=[O:17])[C:9](=[O:14])[NH:10][CH2:11][CH2:12][NH:62][C:61]2[CH:63]=[CH:64][C:58]([O:57][CH:56]([F:65])[F:55])=[CH:59][CH:60]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Nc1ccc(OC(F)F)cc1
Reactant: O=C(N[C@@H](CC1CCCCC1)C(=O)NCCO)c1ccc(-c2cccc(C(F)(F)F)c2)o1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Solvent: CC(=O)O
Product: O=C(N[C@@H](CC1CCCCC1)C(=O)NCCNc1ccc(OC(F)F)cc1)c1ccc(-c2cccc(C(F)(F)F)c2)o1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
(S)-2-Benzyloxycarbonylamino-3-cyclohexyl-propionic acid 1 (2.065 g, 6.77 mmol, 1.0 eq.) was dissolved in CH2Cl2 (50 mL). N-(3-Dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (EDC, 1.56 g, 8.11 mmol, 1.2 eq.) and 1-Hydroxybenzotriazole hydrate (HOBT, 1.10 g, 8.16 mmol, 1.2 eq.) were added to the reaction slurry. After 20 minutes, ethanolamine (1.6 mL, 26.58 mmol, 3.9 eq.) was added via syringe and the reaction was allowed to stir at room temperature and monitored by LC/MS. After the reaction was allowed to proceed to completion, the reaction mixture was extracted with water (40 mL), 1M HCl (30 mL), followed by saturated NaHCO3 and saturated NaCl. The organic layer was dried over MgSO4 and filtered. The organic solvent was removed in vacuo and purified by silica gel chromatography to yield (S)-[2-Cyclohexyl-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-carbamic acid benzyl ester 2 (780 mg, 2.24 mmol, 28%) as a white solid: 1H-NMR (400 MHz, CDCl3) δ 0.76–0.92 (m, 2H), 1.02–1.35 (m, 4H), 1.44–1.73 (m, 7H), 3.17–3.25 (m, 1H), 3.34–3.40 (m, 1H), 3.51–3.69 (m, 3H), 4.24 (dt, 1H, J=8.8 Hz, 5.6 Hz), 4.94 (d, 1H, J=12.0 Hz), 5.07 (d, 1H, J=12.0 Hz), 5.93 (1H, J=12.0 Hz), 7.24–7.30 (m, 5H). Step B: (S)-[2-Cyclohexyl-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-carbamic acid benzyl ester 2 (630 mg, 1.81 mmol) was dissolved in dry MeOH (15 mL) and Pd/C (15 mg, catalytic) was added under N2. The nitrogen atmosphere was replaced with a H2 balloon and allowed to stir at room temperature. The reaction was judged to be complete by LC/MS and the reaction was purged with nitrogen and filtered through celite. The solvent was removed in vacuo to yield (S)-2-Amino-3-cyclohexyl-N-(2-hydroxy-ethyl)-propionamide 3 (380 mg, 1.77 mmol, 98%) as a clear oil: MS calcd. for C11H22N2O2 (M+H+) 215.2. found 215.4. Step C: (S)-2-Amino-3-cyclohexyl-N-(2-hydroxy-ethyl)-propionamide 3 (216 mg, 1.0 mmol, 1.0 eq.), O-(7-Azabenzotrizol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 364 mg, 1.11 mmol, 1.1 eq.), and 5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid (284 mg, 1.11 mmol, 1.1 eq.) was dissolved in CH2Cl2 (10 mL, 0.1 M) and the solution was stirred for 10 min at room temperature. N,N-Diisopropylethylamine (DIPEA, 500 μL, 2.88 mmol, 2.9 eq.) was added and the solution was stirred at room temperature until all stating materials were consumed by LC/MS. The solvent was removed in vacuo and the residue purified by silica gel chromatography (0% to 40% EtOAc gradient in hexanes) to provide (S)-5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid [2-cyclohexyl-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-amide 4 (293 mg, 0.65 mmol, 64%) as a white solid: MS calcd. for C23H27F3N2O4 (M+H+) 453.2. found 453.4. Step D: (S)-5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid [2-cyclohexyl-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-amide 4 (170 mg, 0.38 mmol) was dissolved in CH2Cl2 (5 mL, 0.07M) under a N2 atmosphere. Dess-Martin Periodinane (210 mg, 0.49 mmol, 1.3 eq.) was added in one portion and allowed the reaction to stir at room temperature for 3 hours. After the reaction was judged to be complete by TLC, the reaction was diluted with EtOAc (50 mL) and extracted with 1M sodium thiosulfate (30 mL). The organic layer was extracted with saturated NaHCO3 and saturated NaCl. The organic layer was dried over MgSO4 and filtered. The organic solvent was removed in vacuo and the resulting aldehyde (158 mg, 0.35 mmol, 93%) was used directly without storage: Rf=0.67 (1:1 hexanes:EtOAc). The aldehyde (43 mg, 0.10 mmol) was dissolved in MeOH (2.5 mL, 0.04M) and brought to 0° C. in an ice bath. 4-Difluoromethoxyaniline (50 μL, 0.31 mol, 3.3 eq.) and acetic acid (20 mL, 0.34 mmol, 3.6 eq.) were added via syringe followed by sodium cyanoborohydride (20 mg, 0.32 mmol) in one portion. The clear reaction mixture was allowed to slowly warm to room temperature and monitored to completion by LC/MS. The reaction was worked up by rotary evaporation of MeOH, dilution with EtOAc (20 mL) and water (20 mL). The organic phase was separated and washed with 1M NaOH (15 mL) and saturated NaCl (15 mL). The organic layer was dried over MgSO4, filtered, and concentrated by rotary evaporation. Purification by mass-directed HPLC, evaporation and lyophilization provided (S)-5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid {2-cyclohexyl-1-[2-(4-difluoromethoxy-phenylamino)-ethylcarbamoyl]-ethyl}-amide 5 as a white amorphous solid (15 mg, 0.02 mmol, 22%): 1H NMR (CD3OD, 400 MHz) δ 0.95–1.06 (m, 2H), 1.19–1.29 (m, 3H), 1.40–1.44 (m, 1H), 1.66–1.86 (m, 7H), 3.26–3.29 (m, 2H), 3.43–3.46 (m, 2H), 4.64 (dd, 1H, J=9.2, 6.0 Hz), 6.59 (t, 1H, J=74.8 Hz), 6.76 (d, 2H, J=8.8 Hz), 6.95 (d, 2H, J=8.8 Hz), 7.11 (s, 1H), 7.29 (d, 1H, J=3.6 Hz), 7.66 (s, 2H), 8.13 (s, 1H), 8.25 (s, 1H); HPLC-MS calcd. for C30H32F5N3O4 (M+H+) 594.2. found 594.5.