Hydrochloric Acid → {(R)-1-Hydroxymethyl-2-[4-(4-phenoxy-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester

To a solution of ethanol/tetrahydrofuran (50/50) (2.16 mL), (R)-2-tert-Butoxycarbonylamino-3-[4-(4-phenoxy-phenoxy)-phenyl]-propionic acid methyl ester (0.125 g, 0.324 mmol) was added. Then lithium chloride (0.046 g, 1.296 mmol) and sodium borohydride (0.041 g, 1.296 mmol) dissolved in ethanol/tetrahydrofuran (50/50) (2.16 mL) were added to the reaction mixture. The resulting mixture was stirred starting at 0° C. and warming to room temperature over 18 hours. Reaction was stopped with 1N HCl (1.0 mL) and then extracted with EtOAc (20 mL) and water (15 mL). The organic layer was separated. Organic layer was washed with each and separated for the next wash, 1N HCl (15 mL), sodium bicarbonate (15 mL), and brine (15 mL). The organic layer was then dried over Na2SO4, filtered, and concentrated in vacuo to obtain a crude mixture, which was purified by silica gel flash chromatography, using EtOAc/hexane (gradient system), to obtain the product (0.1 g, 71%): 1H NMR (400 MHz, CDCL3): δ 1.42 (s, 9H), 2.75-2.82 (m, 2H), 3.56-3.70 (m, 2H), 3.85 (s, 1H), 4.73 (s, 1H), 6.94 (d, 2H, J=8.8 Hz), 6.99-7.01 (m, 5H), 7.08 (t, 1H, J=7.2 Hz), 7.17 (d, 2H, J=8.8 Hz), 7.31-7.35 (m, 2H).

1. additionwere added to the reaction mixture
2. customstarting at 0° C.
3. customReaction
4. extractionextracted with EtOAc (20 mL) and water (15 mL)
5. customThe organic layer was separated
6. washOrganic layer was washed with each and
7. customseparated for the next wash, 1N HCl (15 mL), sodium bicarbonate (15 mL), and brine (15 mL)
8. dry with materialThe organic layer was then dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto obtain a crude mixture, which
12. customwas purified by silica gel flash chromatography

ORD record

ord-16af47dbae7446318ce800f491d32384

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989480B2