HCID 131735504, compound → HCID 90358761, compound

HRID 522173Notes

Reaction equation

[Si:1]([O:8][C@@H:9]1[C@@H:14](CP(=O)(OC)OC)[O:13][C@@H:12]([C:22]([F:25])([F:24])[F:23])[C@H:11]2[O:26][C:27]([CH3:30])([CH3:29])[O:28][C@@H:10]12)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si]([O:38][C@@H]1[C@H](CP(=O)(OC)OC)O[C@@H](C(F)(F)F)[C@H]2OC(C)(C)O[C@@H]12)(C(C)(C)C)(C)C>>[Si:1]([O:8][C@@H:9]1[CH:14]([OH:38])[O:13][C@@H:12]([C:22]([F:25])([F:24])[F:23])[C@H:11]2[O:26][C:27]([CH3:29])([CH3:30])[O:28][C@@H:10]12)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]

Participants

Reactant 2

HCID 131735504HCID 131735504, compound

HCID 131735505HCID 131735505, compound

Product 1

HCID 90358761HCID 90358761, compound

Procedure

Dimethyl (((3aS,4R,6S,7S,7aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-4-(trifluoromethyl)tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-6-yl) methyl)phosphonate and dimethyl (((3aS,4R,6R,7S,7aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-4-(trifluoromethyl)tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-6-yl)methyl)phosphonate: In a 25 mL round bottom flask, a stirred solution of (3aS,4R,7S,7aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-4-(trifluoromethyl)tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-6-ol (400 mg, 1.07 mmol, 1eq), in dry THF (10 mL) maintained at 0° C. under nitrogen atmosphere, was treated with LiHMDS (1M in THF, 0.39 mL, 3.22 mmol, commercially available from Sigma Aldrich, India) at 0° C. The reaction mixture was stirred at 0° C. for 30 min under a nitrogen atmosphere and treated with tetramethyl methylenebis(phosphonate) (800 mg, 3.22 mmol, Alfa Asear, India) in THF (8 mL) at the same temperature. The resulting reaction mixture was stirred at rt for 36 h. Upon completion of the reaction (TLC, 30% EtOAc in hexane, Rf 0.4), the reaction mixture was quenched with saturated NaHCO3 solution at 0° C. and stirred for 5 min. The mixture was diluted with water (40 mL) and extracted with EtOAc (2×20 mL). The organic extract was washed with water, brine (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue obtained was purified by silica gel (60-120 mesh) column chromatography (gradient elution 5-10% EtOAc-hexanes) to give dimethyl (((3aS,4R,6S,7S,7aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-4-(trifluoromethyl)tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-6-yl)methyl)phosphonate and dimethyl (((3aS,4R,6R,7S,7aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-4-(trifluoromethyl)tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-6-yl)methyl)phosphonate as a sticky oils. Dimethyl (((3aS,4R,6S,7S,7aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-4-(trifluoromethyl)tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-6-yl)methyl)phosphonate (100 mg, 20%): 1H NMR (400 MHz, CDCl3) δ 4.34-4.32 (m, 1H), 4.22-4.17 (m, 1H), 4.06 (t, J=6.0 Hz 1H), 3.74-3.69 (m, 7H), 3.60 (t, J=7.2 Hz 1H), 2.38-2.29 (m, 1H), 2.06-1.95 (m, 1H), 1.52 (s, 3H), 1.35 (s, 3H), 0.9 (s, 9H), 0.13 (s, 3H), 0.06 (s, 3H); 19F NMR (376.17 MHz, CDCl3) δ −72.32 ppm. Dimethyl (((3aS,4R,6R,7S,7aR)-7-((tert-butyldimethylsilyl)oxy)-2,2-dimethyl-4-(trifluoromethyl)tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-6-yl)methyl)phosphonate (70 mg, 14%): 1H NMR (400 MHz, CDCl3) δ 4.50-4.42 (m, 1H), 4.39-4.32 (m, 1H), 4.22-4.18 (m, 1H), 4.11-4.04 (m, 1H), 3.82 (m, 1H), 3.76-3.70 (m, 6H), 2.14-1.87 (m, 2H), 1.52 (s, 3H), 1.35 (s, 3H), 0.9 (s, 9H), 0.13 (s, 3H), 0.06 (s, 3H) ppm.

Sources & evidence

ORD record: ord-10de68995c6545858906a674655a9c4f
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328134B2

Reaction notes

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