4-Nitrobenzoic Acid → 3-(Ethoxycarbonyl)-4-ethylcyclopentyl 4-nitrobenzoate

To triphenylphosphine (34.9 g, 133 mmol) in THF (150 mL) at about 0° C. was added a solution of DIAD (26.2 mL, 133 mmol) in THF (20 mL) through an additional funnel. After about 30 min, a solution of 4-nitrobenzoic acid (22.26 g, 133 mmol) in THF (150 mL) was added followed by a solution of a scalemic mixture enriched with (1S,2R,4S)-ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate (16.54 g, 89 mmol) in THF (20 mL) and triethylamine (55.7 mL, 400 mmol). After about 1 h, the ice water bath was removed and the reaction mixture was stirred at ambient temperature for about 16 h. The reaction mixture was diluted with heptane (800 mL), washed with water (200 mL), saturated aqueous NaHCO3 (150 mL) and brine (150 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. After about 300 mL of solvent was removed, the solid was filtered off and washed with heptane (25 mL). The filtrate was concentrated under reduced pressure and the residue was purified using silica gel chromatography eluting with 10-40% EtOAc in heptane to give a scalemic mixture enriched with (1R,3S,4R)-3-(ethoxycarbonyl)-4-ethylcyclopentyl 4-nitrobenzoate (26.77 g, 90%): LC/MS (Table 1, Method b) Rt=2.84 min; MS m/z: 394 (M−H)−.

1. waitAfter about 1 h
2. customthe ice water bath was removed
3. additionThe reaction mixture was diluted with heptane (800 mL)
4. washwashed with water (200 mL), saturated aqueous NaHCO3 (150 mL) and brine (150 mL)
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. customAfter about 300 mL of solvent was removed
8. filtrationthe solid was filtered off
9. washwashed with heptane (25 mL)
10. concentrationThe filtrate was concentrated under reduced pressure
11. customthe residue was purified
12. washeluting with 10-40% EtOAc in heptane
13. customto give a scalemic mixture

ORD record

ord-6e1beaf82088427aa6a6e6a8781de43e

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2