Reaction SMILES: [I-].C[S+](C)(C)=O.[CH3:7]C(C)([O-])C.[K+].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C@@:20]2([OH:44])[CH2:25][CH2:24][N:23]([C:26](=[O:41])[C@H:27]([NH:31][C:32]([CH:34]3[CH2:40][CH2:39][C:36]4([O:38][CH2:37]4)[CH2:35]3)=[O:33])[CH:28]([CH3:30])[CH3:29])[CH2:22][C:21]2([CH3:43])[CH3:42])=[CH:16][CH:15]=1>C(O)(C)(C)C>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C@@:20]2([OH:44])[CH2:25][CH2:24][N:23]([C:26](=[O:41])[C@H:27]([NH:31][C:32]([CH:34]3[CH2:40][CH2:39][C:36]4([O:38][CH2:7][CH2:37]4)[CH2:35]3)=[O:33])[CH:28]([CH3:30])[CH3:29])[CH2:22][C:21]2([CH3:42])[CH3:43])=[CH:16][CH:15]=1
Reactant: CC(C)[C@@H](NC(=O)C1CCC2(CO2)C1)C(=O)N1CC[C@](O)(c2ccc(Cl)cc2)C(C)(C)C1
Reactant: CC(C)(C)[O-]
Agent: C[S+](C)(C)=O
Agent: [I-]
Agent: [K+]
Solvent: CC(C)(C)O
Product: CC(C)[C@@H](NC(=O)C1CCC2(CCO2)C1)C(=O)N1CC[C@](O)(c2ccc(Cl)cc2)C(C)(C)C1
Temperature: 50 °C
Reaction time: 48 h

Procedure:
A suspension of trimethylsulfoxonium iodide (67.8 mg, 0.308 mmol) in tert-butanol (2 mL) was treated with potassium tert-butoxide (34.6 mg, 0.308 mmol). The mixture was heated at 50° C. for 1 hour, then treated with N—((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-1-oxaspiro[2.4]heptane-5-carboxamide (46 mg, 0.099 mmol), and the reaction was stirred at 50° C. for 2 days. The reaction was quenched with saturated ammonium chloride (1 mL), and the mixture was poured into ethyl acetate (15 mL). The layers were separated, and the organic phase was washed 3× with water and once with brine, then dried over sodium sulfate and concentrated in vacuo. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters SunFire C18, 19×150 mm, 5 μm particles; Guard Column. None; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 15-100% B over 15 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the desired product as a diastereomeric mixture was 15.4 mg, and its purity was 96%. Two analytical LC/MS injections were used to determine the final purity. Injection 1 conditions: Column: Supelco Ascentis Express C18, 4.6×50 mm, 2.7-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 45° C.; Gradient: 0-100% B over 5.3 minutes, then a 1.7-minute hold at 100% B; Flow: 3 mL/min. Retention time=2.91. Injection 2 conditions: Column: Waters XBridge C18, 4.6×50 mm, 2.5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% ammonium hydroxide; Mobile Phase B: 95:5 acetonitrile:water with 0.1% ammonium hydroxide; Temperature: 45° C.; Gradient: 0-100% B over 7 minutes, then a 1-minute hold at 100% B; Flow: 3 mL/min. Retention time=3.79 minutes. Proton NMR was acquired in deuterated methanol. MS (ESI+)=476.9 (M+H)+. 1H NMR (400 MHz, CD3OD) (NMR shows several rotomers) δ ppm 7.53-7.42 (m, 2H), 7.36-7.26 (m, 2H), 4.83-4.76 (m, 1H), 4.58-4.42 (m, 2H), 4.13-3.98 (m, 1H), 3.66-3.58 (bd, 1H, J=13.3 Hz), 3.58-3.46 (m, 1H), 3.22-3.06 (m, 1H), 2.95-2.86 (m, 0.4H), 2.83-2.56 (m, 3.2H), 2.38-1.69 (m, 7H), 1.59 (d, 0.5H, J=14.3 Hz), 1.51 (d, 0.5H, J=14.6 Hz), 1.47-1.42 (m, 0.2H), 1.04 (d, 1.5H, J=6.5 Hz), 0.98 (t, 1.5H, J=6.2 Hz), 0.92 (d, 3H, J=5.3 Hz), 0.81 (d, 3H, J=4.8 Hz), 0.75 (br. s, 3H.).