Sodium Thiosulfate Pentahydrate → [(2R,4R,5S)-5-amino-2-((benzyloxy)methyl)-5-(5-bromo-2,4-difluorophenyl)tetrahydro-2H-pyran-4-yl]methanol

To C6 (1.0 g, 2.27 mmol) in tetrahydrofuran (1 mL) cooled to 0° C. was added a tetrahydrofuran solution of samarium iodide (0.1 M, 90.8 mL, 9.08 mmol) in a drop-wise manner. The resulting solution was allowed to stir at room temperature for 90 minutes. A saturated aqueous solution of sodium thiosulfate pentahydrate (1 L) was added to the reaction, followed by extraction with ethyl acetate (3×250 mL). The combined organics were washed with brine (1×500 mL), dried over sodium sulfate, filtered and concentrated in vacuo to afford a clear oily residue. The residue was dissolved in dichloromethane (5 mL) and filtered through a silica gel plug (approx 100 g) with dichloromethane (3×100 mL). The combined filtrates were concentrated in vacuo to afford the product as a clear oily residue, which was used directly in the next step. Yield: 947 mg, 2.14 mmol, 94%. LCMS m/z 443.1 [M+H+], Br isotopic pattern. 1H NMR (400 MHz, CD3OD), characteristic peaks: δ 8.00 (t, J=8.1 Hz, 1H), 7.24-7.38 (m, 5H), 7.10 (dd, J=12.1, 8.4 Hz, 1H), 4.58 (s, 2H), 4.03 (dd, J=11.2, 2.2 Hz, 1H), 3.72-3.80 (m, 1H), 3.56-3.64 (m, 2H), 3.44 (d, J=11.3 Hz, 1H), 3.34, (d, J=5.1 Hz, 1H), 2.46-2.53 (m, 1H), 1.68-1.80 (m, 2H).

1. extractionfollowed by extraction with ethyl acetate (3×250 mL)
2. washThe combined organics were washed with brine (1×500 mL)
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto afford a clear oily residue
7. filtrationfiltered through a silica gel plug (approx 100 g) with dichloromethane (3×100 mL)
8. concentrationThe combined filtrates were concentrated in vacuo
9. customto afford the product as a clear oily residue, which

ORD record

ord-018bca32798f43ad9cda4e882c2b1e21

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822456B2