Reaction SMILES: C(OC([NH:8][C@H:9]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:10]COS(C)(=O)=O)=O)(C)(C)C.[F:23][C:24]1[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:25]=1[C:32]1[C:33](=[O:52])[NH:34][C:35](=[O:51])[N:36]([CH2:39][C:40]2[C:45]([C:46]([F:49])([F:48])[F:47])=[CH:44][CH:43]=[CH:42][C:41]=2[F:50])[C:37]=1[CH3:38].CN(C)C(N(C)C)=N.OP(O)(O)=O.O.C(OC(C)C)(=O)C>CN(C=O)C>[NH2:8][C@H:9]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:10][N:34]1[C:33](=[O:52])[C:32]([C:25]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:24]=2[F:23])=[C:37]([CH3:38])[N:36]([CH2:39][C:40]2[C:45]([C:46]([F:48])([F:49])[F:47])=[CH:44][CH:43]=[CH:42][C:41]=2[F:50])[C:35]1=[O:51]
Reactant: COc1cccc(-c2c(C)n(Cc3c(F)cccc3C(F)(F)F)c(=O)[nH]c2=O)c1F
Reactant: CC(C)(C)OC(=O)N[C@@H](CCOS(C)(=O)=O)c1ccccc1
Agent: CN(C)C(=N)N(C)C
Agent: O=P(O)(O)O
Solvent: CC(=O)OC(C)C
Solvent: O
Solvent: CN(C)C=O
Product: COc1cccc(-c2c(C)n(Cc3c(F)cccc3C(F)(F)F)c(=O)n(C[C@H](N)c3ccccc3)c2=O)c1F
Temperature: 40 °C
Yield: 83.5 %

Procedure:
Methanesulfonic acid (S)-3-tert-butoxycarbonylamino-3-phenyl-propyl ester 1d (177.54 g), 5-(2-fluoro-3-methoxy-phenyl)-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione 1c (160.0 g), 1,1,3,3-tetramethylguanidine (117.72 mL) and DMF (320 mL) were charged to a reactor. The mixture was stirred at 40° C. After reaction completion (48 hr), 85% H3PO4/water (129.8 g/960 mL) was added followed by isopropyl acetate (960 mL). After agitation and settling, the layers were separated and the organic layer washed with 85% H3PO4/water (43.27 g/48 mL). After agitation and settling, the aqueous layer was removed and the organic layer washed with water (480 mL). After agitation and settling, the aqueous layer was removed. To the organic layer was charged water (76 mL) and methanesulfonic acid (108.2 g) and the reactor contents were heated to 60° C. for 6 hours. The reactor contents were cooled to 40° C. and a solution of potassium carbonate/water (259.34 g/1360 mL) was added slowly, agitated, and then allowed to settle prior to separation of layers. The organic layer was treated with a solution of 85% phosphoric acid/H2O (129.81 g/1360 mL). The mixture was agitated, allowed to settle, and the layers were separated. The aqueous layer was washed with isopropyl acetate (2×1120 mL) and the layers were separated. A solution of potassium carbonate/water (259.34 g/480 mL) was added slowly to the aqueous layer. Isopropyl acetate (1360 mL) was charged; the mixture was agitated and then allowed to settle. The aqueous layer was removed and the organic layer was washed with water (480 mL) and the layers were separated. The organic later was filtered through a medium glass frit and the lines/filter were rinsed with 220 mL i-PrOAc. The organic layer was concentrated by distillation to approximately 550-750 mL volume. This solution was heated at 80° C. and heptane (640 mL) was added over one hour. NBI-54048 crystalline seeds (2.0 g) were charged after approximately one third of the heptane charge was complete. After heptane addition the mixture was maintained at 80° C. for 2 hr, then cooled to 10° C. over 180 min. The mixture was filtered to provide a solid that was dried under vacuum at 50-60° C. overnight. 3-((R)-2-amino-2-phenyl-ethyl)-5-(2-fluoro-3-methoxy-phenyl)-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione 1e (170.9 g, 84% yield) was obtained as a white solid. LCMS (ESI) m/z 546.2 (MH+)