Acetic Acid → t-Butyldimethylsilyl 3-O-allyloxycarbonyl-6-O-benzyl-2-deoxy-4-O-(1,5-dihydro-3-oxo-3lambda5-3H-2,4,3-benzodioxaphosphepin-3-yl)-2-(9-fluorenylmethoxycarbonylamino)-beta-D-glucopyranoside

Acetic acid (300 μL, 5.20 mmol) was added dropwise to a stirred suspension of 10 (1.40 g, 2.08 mmol) and zinc powder (676 mg, 10.4 mmol) in DCM (15 mL). The reaction mixture was stirred at room temperature for 2 h, after which it was diluted with ethyl acetate (50 mL). The solids were removed by filtration and washed with ethyl acetate (2×10 mL). The combined filtrates were washed with saturated aqueous NaHCO3 (2×40 mL) and brine (2×40 mL). The organic phase was dried (MgSO4), filtered, and the filtrate was concentrated in vacuo to afford a crude amine as a pale yellow oil. Rf=0.21 (hexane/ethyl acetate, 1/1, v/v). FmocCl (645 mg, 2.50 mmol) was added to a stirred solution of the crude amine and DIPEA (435 μL, 2.50 mmol) in DCM (15 mL) at 0° C. The reaction mixture was stirred at room temperature for 5 h, after which it was diluted with DCM (40 mL) and washed with brine (2×50 mL). The organic phase was dried (MgSO4) and filtered. Next, the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/ethyl acetate, 4/1-2/1, v/v) to afford 11 as a colorless solid (1.45 g, 80% over two steps). Rf=0.54 (hexane/ethyl acetate, 1/1, v/v). [α]25D=−3.9° (c=1.0, CDCl3); 1H NMR (500 MHz, CDCl3): δ 7.78-7.20 (m, 17H, aromatic), 5.92-5.82 (m, 1H, OCH2CH═CH2), 5.42 (broad, 1H, H-3), 5.31 (d, 1H, J=17.6 Hz, OCH2CH═CH2), 5.20-5.07 (m, 6H, H-1, OCH2CH═CH2, C6H4(CH2O)P), 4.67-4.56 (m, 5H, H-4, OCH2CH═CH2, CH2Ph), 4.41-4.23 (m, 3H, COOCH2, Fmoc, COOCH2CH, Fmoc), 3.89-3.87 (broad, 1H, H-6a), 3.76-3.74 (broad, 2H, H-5, H-6b), 3.49-3.47 (m, 1H, H-2), 0.88 (s, 4H, SiC(CH3)3), 0.14 (s, 3H, Si(CH3)2), 0.10 (s, 3H, Si(CH3)2). 13C NMR (75 MHz, CDCl3): δ 155.52 (C═O), 154.80 (C═O), 143.71-119.94 (aromatic), 131.34 (OCH2CH═CH2), 118.85 (OCH2CH═CH2), 95.41 (C-1), 74.77 (C-4), 73.85 (C-5), 73.47 (CH2Ph), 68.94, 68.57, 68.50, 68.42 (C-3, C-6, OCH2CH═CH2, OC6H4(CH2O)P), 68.50 (OC6H4(CH2O)P), 67.12 (CO2CH2CH, Fmoc), 58.69 (C-2), 47.04 (CO2CH2CH, Fmoc), 25.52 (SiC(CH3)3), 17.88 (SiC(CH3)3), −4.26 (Si(CH3)2), −5.38 (Si(CH3)2). HR MS (m/z) calculated for C46H54NO12PSi[M+Na]+, 894.3051. found, 894.3937.

1. customThe solids were removed by filtration
2. washwashed with ethyl acetate (2×10 mL)
3. washThe combined filtrates were washed with saturated aqueous NaHCO3 (2×40 mL) and brine (2×40 mL)
4. dry with materialThe organic phase was dried (MgSO4)
5. filtrationfiltered
6. concentrationthe filtrate was concentrated in vacuo
7. customto afford a crude amine as a pale yellow oil
8. stirringThe reaction mixture was stirred at room temperature for 5 h
9. washwashed with brine (2×50 mL)
10. dry with materialThe organic phase was dried (MgSO4)
11. filtrationfiltered
12. concentrationNext, the filtrate was concentrated in vacuo
13. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate, 4/1-2/1

ORD record

ord-7f5f8e76010248f68d8b22e95eb8d9f0

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309276B2