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A stirred off-white suspension of 1-[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]ethanone (55.6 mg, 0.113 mmol) in THF (2.3 ml) was degassed (3×) and placed under nitrogen before being cooled to 0° C. in an ice bath. Ethylmagnesium bromide 3.0 M in diethyl ether (0.38 ml, 1.140 mmol) was added to the reaction mixture dropwise, to give a green suspension. After a few minutes, the reaction mixture was removed from the ice bath and allowed to warm to room temperature. After 2 hours, the reaction mixture was pipetted into saturated aqueous NaHCO3 (30 ml). The resulting biphasic suspension was partitioned between EtOAc (30 ml) and water (10 ml). The aqueous layer was extracted with EtOAc (2×20 ml). The organic layers were combined, washed with brine (1×20 ml), dried over Na2SO4, filtered, and evaporated under reduced pressure to give a green residue. This material was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile+0.05% TFA flush. The product fractions were combined and evaporated under reduced pressure to give the racemic product as a colorless residue, which was separated by preparative HPLC Chiralpak AD™, eluting with 30% isopropanol/heptane at 9 mL/minute. The fractions from the faster eluting peak were collected, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give isomer A of the title compound as a white solid. LC-MS: calculated for C28H28ClN3O5 521.17 observed m/e: 522.23 (M+H)+ (Rt 1.16/2 min); 1H NMR δ (ppm) (CD3OD): 7.82 (s, 1H), 7.73 (s, 4H), 7.66 (d, J=8.5 Hz, 2H), 7.54 (d, J=8.5 hz, 2H), 5.54 (qt, Hz=5.4 Hz, 1H), 4.96 (t, J=5.2 Hz, 1H), 4.47 (t, J=5.0 Hz, 1H), 4.26-4.30 (m, 1H), 4.17 (dd, J=5.8 Hz, J=10.2 Hz, 1H), 4.10 (dd, J=4.9 Hz, 10.2 Hz, 1H), 3.90 (dd, J=6.9 Hz, J=8.1 Hz, 1H), 3.60 (t, J=8.6 Hz, 1H), 1.83-1.88 (m, 2H), 1.55 (s, 3H), 0.82 (t, J=7.4 Hz, 3H).

1. customwas degassed (3×)
2. customto give a green suspension
3. waitAfter a few minutes
4. customthe reaction mixture was removed from the ice bath
5. temperatureto warm to room temperature
6. customThe resulting biphasic suspension was partitioned between EtOAc (30 ml) and water (10 ml)
7. extractionThe aqueous layer was extracted with EtOAc (2×20 ml)
8. washwashed with brine (1×20 ml)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customevaporated under reduced pressure
12. customto give a green residue
13. customThis material was purified by preparative HPLC reverse phase (C-18)
14. washeluting with a 20%-100% acetonitrile/water+0.05% TFA
15. customflush
16. customevaporated under reduced pressure
17. customto give the racemic product as a colorless residue, which
18. customwas separated by preparative HPLC Chiralpak AD™
19. washeluting with 30% isopropanol/heptane at 9 mL/minute
20. washThe fractions from the faster eluting peak
21. customwere collected
22. customevaporated under reduced pressure