tert-Butanol → HCID 11317948, compound

Temperature

35 °C

Under a nitrogen atmosphere, a solution of 4 (274 mg, 0.67 mmol), n-Bu3SnCl (57 μL, 0.21 mmol, 0.3 equiv.), NaBH3CN (95% grade, 65 mg, 1.04 mmol, 1.5 equiv.), diethyl vinylphosphonate (1.1 mL, 6.91 mmol, 10 equiv.), ABCN (110 mg, 0.45 mmol, 0.67 equiv.), and tert-butanol (0.65 mL, 6.91 mmol, 10 equiv.) in diethylether (5 mL) was stirred at reflux temperature (35° C.). After 4 days, TLC (cyclohexane/EtOAc 1:1) showed complete consumption of the starting material and the formation of two new species, the desired diethyl 2-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-ethylphosphonate 5a (Rf 0.1) and side product 2,3,4,6-tetra-O-acetyl-β-D-glucopyranose 5b (Rf 0.47). The reaction was concentrated in vacuo, and the oily residue was dissolved in CH2Cl2 (30 mL). The organic solution was washed with water (3×30 mL), dried over MgSO4, and reduced to dryness. The residue was purified by chromatography on a silica gel column, which was eluted first with cyclohexane/EtOAc (1:1) and then with EtOAc/EtOH (20:1), to afford 5a as a syrup (257 mg, 71%): Rf 0.5 (EtOAc/EtOH 20:1); δH (400 MHz, CDCl3) 5.37 (dd, 1H, J5,6 3.0 Hz, J6,7 2.8 Hz, H-6), 5.24 (dd, 1H, J3,4 5.2 Hz, J4,5 9.3 Hz, H-4), 5.14 (dd, 1H, J5,6 3.3 Hz, J4,5 9.5 Hz, H-5), 4.22-4.00 (m, 7H, H-3, H-8a, H-8b, 2 OCH2CH3), 3.97 (m, 1H, H-7), 2.09, 2.04, 2.01, 1.98 (all s, 12H, 4×C(O)CH3), 2.98-1.56 (m, 4H, H-1a, H-1b, H-2a, H-2b), 1.29 (dt, 6H, 4JH,P 2.8 Hz, JH,H 7.0 Hz, 2 OCH2CH3); δC (100 MHz, CDCl3) 170.4, 170.0, 169.9, 169.8 (4×C═O), 72.9 (d, JC,P 17.0 Hz, C-3), 68.3 (C-7), 68.2 (C-4), 67.9 (C-5), 67.6 (C-6), 61.8 (d, 2JC,P 6.0 Hz, OCH2CH3), 61.7 (d, 2JC,P 5.0 Hz, OCH2CH3), 61.5 (C-8), 22.1 (C-1), 20.7 (4×C(O)CH3), 19.3 (C-2), 16.4 (d, JC,P 6.0 Hz, 2×OCH2CH3); δP (161.9 MHz, CDCl3) 32.0. m/z (ESI) 497.1772 [M+H]+, C20H33O12P requires 497.1782. 5b: Rf 0.47 (cyclohexane/EtOAc 1:1); δH (400 MHz, CDCl3) 5.35 (dd, 1H, J3,4 3.4 Hz, J6,7<1.0 Hz, H-4), 5.11 (dd, 1H, J1a,2 5.5 Hz, J1b,2 10.3 Hz, J2,3 10.3 Hz, H-2), 4.95 (dd, 1H, H-3), 4.10 (dd, 1H, J1a,1b 11.1 Hz, H-1a), 4.00 (d, 2H, J5,6 6.4 Hz, H-6a, H-6b), 3.74 (t, 1H, H-5), 3.20 (dd, 1H, H-1b), 2.06, 1.97, 1.96, 1.91 (all s, 12H, 4×C(O)CH3); δC (100 MHz, CDCl3) 170.6, 170.4, 170.3, 170.1 (4×C═O), 75.0 (C-5), 71.6 (C-3), 67.9 (C-4), 67.2 (C-1), 66.5 (C-2), 62.2 (C-6), 20.9, 20.8 (4×C(O)CH3). m/z (ESI) 350.1445 [M+NH4]+, C14H2O9 requires 350.1446.

1. customconsumption of the starting material
2. concentrationThe reaction was concentrated in vacuo
3. dissolutionthe oily residue was dissolved in CH2Cl2 (30 mL)
4. washThe organic solution was washed with water (3×30 mL)
5. dry with materialdried over MgSO4
6. customThe residue was purified by chromatography on a silica gel column, which
7. washwas eluted first with cyclohexane/EtOAc (1:1)

ORD record

ord-daa0cce1730c4ed491b488706b7c3b30

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018370B2