Reaction SMILES: O[CH:2]([C:20]1[C:21]([CH3:30])=[C:22]2[C:26](=[CH:27][CH:28]=1)[C:25](=[O:29])[O:24][CH2:23]2)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH:5]1[CH2:17][CH2:18][OH:19].C(C=P(CCCC)(CCCC)CCCC)#N>C1C=CC=CC=1>[CH3:30][C:21]1[C:22]2[CH2:23][O:24][C:25](=[O:29])[C:26]=2[CH:27]=[CH:28][C:20]=1[CH:2]1[CH2:3][N:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[CH2:6][CH:5]2[CH2:17][CH2:18][O:19]1
Reactant: Cc1c(C(O)CN2CCN(C(=O)OC(C)(C)C)CC2CCO)ccc2c1COC2=O
Agent: CCCCP(=CC#N)(CCCC)CCCC
Solvent: c1ccccc1
Product: Cc1c(C2CN3CCN(C(=O)OC(C)(C)C)CC3CCO2)ccc2c1COC2=O
Temperature: 100 °C
Reaction time: 0.13 h

Procedure:
tert-Butyl 4-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-(2-hydroxyethyl)piperazine-1-carboxylate (2.22 g, 5.30 mmol) was dissolved in benzene (30 mL) and then cyanomethylene tributyl phosphorane (2.31 g, 9.55 mmol) was added, which was then heated to 100° C. overnight. The benzene was removed by rotary evaporation, and the residue was chromatographed through an ISCO redi-sep 330 g column and eluted with 15% acetone:85% DCM. This separated the cis-diastereomers from the trans-diastereomers of the title compound. The cis-diastereomers were further separated to S,S and R,R diastereomers using the following conditions: Chiralpak AD column: 30×250 mm, 30% (2:1 MeOH:CH3CN)/CO2, 70 mL/min, 100 bar, 41 mg/mL in MeOH/MeCN/DCM, 35° C., 254 nm: cis-diastereomer A (retention time 3.2 mins): 1H-NMR (500 MHz, CDCl3) δ ppm 7.83 (d, J=8 HZ, 1H), 7.78 (d, J=8 Hz, 1H), 5.27 (s, 2H), 4.97 (dd, J=4.75, 2.8 Hz, 1H), 4.13 (t, J=3.45 Hz, 0.5H), 4.10 (t, J=3.45 Hz, 0.5H), 3.91 (t, J=12 Hz, 1H), 3.82 (b, 2H), 3.17 (d, J=5.3 Hz, 0.5H), 3.13 (d, J=5.1 Hz, 0.5H), 2.93 (d, J=2.9 Hz, 0.5H), 2.90 (d, J=2.9 Hz, 0.5H), 2.88 (b, 1H), 2.69 (b, 4H), 2.31 (s, 3H), 1.89-1.92 (m, 2H), 1.49 (s, 9H): cis-diastereomer B (retention time 4.21 min): 1H-NMR (500 MHz, CDCl3) δ ppm 7.83 (d, J=8 HZ, 1H), 7.78 (d, J=8 Hz, 1H), 5.27 (s, 2H), 4.97 (dd, J=4.75, 2.75 Hz, 1H), 4.13 (t, J=3.45 Hz, 0.5H), 4.10 (t, J=3.45 Hz, 0.5H), 3.91 (t, J=10.12 Hz, 1H), 3.82 (b, 2H), 3.17 (d, J=5.1 Hz, 0.5H), 3.14 (d, J=5.1 Hz, 0.5H), 2.93 (d, J=2.9 Hz, 0.5H), 2.90 (d, J=2.9 Hz, 0.5H), 2.88 (b, 1H), 2.69 (b, 4H), 2.31 (s, 3H), 1.89-1.92 (m, 2H), 1.49 (s, 9H): The trans-diastereomers were further separated to the S,R and R,S diastereomers using the following condition: Chiralpak AD column: 30×250 mm, 20% (2:1 MeOH:CH3CN)/CO2, 70 ml/min, 100 bar, 33 mg/mL in MeOH/MeCN/DCM, 35° C., 254 nm. The retention times of trans-diastereomer A and trans-diastereomer B were 6.68 mins and 8.08 mins on the analytical column Chiralpak AD: 4.6×250 mm, 15% (2:1 MeOH: CH3CN)/CO2, 2.1 ml/min, 100 bar, 35° C. 254 nm: trans-diastereomer A: 1H-NMR (500 MHz, CDCl3) δ ppm 7.78 (d, J=8 HZ, 1H), 7.69 (d, J=8 Hz, 1H), 5.27 (s, 2H), 5.13 (d, J=8.8 Hz, 1H), 3.99-4.12 (m, 2H), 3.78-3.95 (b, 2H), 3.02 (b, 1H), 2.87 (d, J=9.1 Hz, 0.5H), 2.84 (d, J=9.0 Hz, 0.5H), 2.77 (b, 2H), 2.65 (d, J=14.5 Hz, 1H), 2.40-2.44 (m, 2H), 2.34 (s, 3H), 2.02-2.08 (m, 1H), 1.92-1.98 (m, 1H), 1.50 (s, 9H): trans-diastereomer B: 1H-NMR (500 MHz, CDCl3) δ ppm 7.78 (d, J=8 HZ, 1H), 7.68 (d, J=8 Hz, 1H), 5.27 (s, 2H), 5.13 (d, J=8.8 Hz, 1H), 4.00-4.12 (m, 2H), 3.98 (b, 2H), 3.01 (b, 1H), 2.86 (d, J=9.1 Hz, 0.5H), 2.83 (d, J=9.0 Hz, 0.5H), 2.76 (b, 2H), 2.65 (d, J=13 Hz, 1H), 2.40-2.44 (m, 2H), 2.34 (s, 3H), 2.03-2.08 (m, 1H), 1.94-1.97 (m, 1H), 1.50 (s, 9H).