Reaction SMILES: C(OC(=O)[NH:7][C@@H:8]([CH2:14][N:15](C(OCC1C=CC=CC=1)=O)[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[CH3:24])[C@@H:9]([OH:13])[CH2:10][CH2:11][CH3:12])(C)(C)C>CO.[Pd]>[NH2:7][C@H:8]([C@@H:9]([OH:13])[CH2:10][CH2:11][CH3:12])[CH2:14][NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[CH3:24]
Reactant: CCC[C@H](O)[C@H](CN(Cc1ccc(C)cc1C)C(=O)OCc1ccccc1)NC(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CO
Product: CCC[C@H](O)[C@@H](N)CNCc1ccc(C)cc1C
Temperature: 25 °C
Reaction time: 12 h
Yield: 106.8 %

Procedure:
To a solution of 2,2-difluoro-malonic acid diethyl ester (500 mg, 2.5 mmol) in EtOH (10 mL) was added KOH (82 mg, 2.0 mmol). The resultant suspension was stirred overnight and then concentrated in vacuo to provide the potassium salt of 2,2-difluoro-malonic acid ethyl ester (208 mg, 40% yield). This material (1.0 mmol) was dissolved in 9 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with meta-trifluoromethylaniline (0.13 mL, 1.0 mmol), N,N-diisopropylethylamine (0.9 mL, 5.0 mmol) and HATU (460 mg, 1.2 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo to provide 2,2-difluoro-N-(3-trifluoromethyl-phenyl)-malonamic acid ethyl ester. MS found: (M−H)−=310.2. (26b) A solution of (1S,2S)-(1-{[benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl)-carbamic acid tert-butyl ester (600 mg, 1.2 mmol, see procedure 12a) in MeOH was charged with 5% Pd/C, Degussa style (120 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. The residue was dissolved in methylene chloride (6 mL) and the resultant solution was charged with trifluoroacetic acid (6 mL). The mixture was stirred for 3 h at RT and concentrated in vacuo. The residue was dissolved in benzene and the resultant solution was concentrated in vacuo; this procedure was repeated to provide (2S,3S)-2-amino-1-(2,4-dimethyl-benzylamino)-hexan-3-ol (321 mg). MS found: (M+H)+=251.4. (26c) The compound 2,2-difluoro-N-(3-trifluoromethyl-phenyl)-malonamic acid ethyl ester (314 mg, 1.0 mmol) was dissolved in THF (6 mL). The resultant solution was charged sequentially with MeOH (2 mL) and aq. LiOH (24 mg LiOH in 2 mL water). The mixture was concentrated in vacuo, and the residue was lyophilized from 1:1 acetonitrile/water to provide the lithium salt of 2,2-difluoro-N-(3-trifluoromethyl-phenyl)-malonamic acid. A portion (106 mg, 0.4 mmol) of this material was dissolved in 4 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with (2S,3S)-2-amino-1-(2,4-dimethyl-benzylamino)-hexan-3-ol (71 mg, 0.2 mmol, see procedure 26b), N,N-diisopropylethylamine (0.37 mL, 2.1 mmol) and HATU (194 mg, 0.51 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification of the residue by reverse-phase HPLC provided the title compound as a white powder after lyopholization. MS found: (M+H)+=516.3.