Acetonitrile--water (1/1) → (+)-(1R,2S,5R)-5-(hydroxymethyl)cyclopent-3-ene-1,2-diyl dibenzoate

To a well stirred solution of (−)-(1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diyl dibenzoate hydrochloride (6) (10.0 g, 25.5 mmol) in mixture of acetonitrile/water (1:1) was added sodium nitrite (8.8 g, 127.8 mmol) by portion wise at 0° C. After 15 minutes 50% aqueous acetic acid solution was added drop wise over a period of 0.5 hr and the mixture was vigorously stirred for 2 hr. The organic solvent was removed under reduced pressure and the rest of mixture was quenched with water. The aqueous phase was extracted with EtOAc (50 mL×3). The combined organic layers were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The residue was purified by flash silica gel column chromatography (20% EtOAc/hexane) to give compound 7. [α]24D −156° (c 1.0, CHCl3); 1H NMR (500 MHz, DMSO-d6): δ 8.05 (m, 2H), 7.89 (m, 2H), 7.52 (m, 2H), 7.38 (m, 2H), 7.28 (m, 2H), 6.11 (m, 3H), 5.54 (m, 1H), 3.87-3.82 (m, 2H), 3.27 (m, 1H), 2.29 (m, 1H). HR-MS Calcd. For (C25H29NO7+H)+ 339.1154, found 339.1286.

1. customThe organic solvent was removed under reduced pressure
2. customthe rest of mixture was quenched with water
3. extractionThe aqueous phase was extracted with EtOAc (50 mL×3)
4. dry with materialThe combined organic layers were dried over Na2SO4
5. filtrationfiltered
6. customthe solvent was removed under reduced pressure
7. customThe residue was purified by flash silica gel column chromatography (20% EtOAc/hexane)

ORD record

ord-bb9d925438d942b0b12b92aa0ded3bb4

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08673926B2