Nitric Acid → methyl (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentanecarboxylate

HRID 2067141Notes

Reaction equation

HRID 2067141 reaction equation
[N+:1]([O-:4])([OH:3])=[O:2].O[C@H:6]1[C@H:10]([O:11][CH3:12])[CH2:9][C@H:8]([C:13]([O:15][CH3:16])=[O:14])[CH2:7]1.C(=O)([O-])O.[Na+]>C(OC(=O)C)(=O)C>[CH3:12][O:11][C@@H:10]1[C@@H:6]([O:2][N+:1]([O-:4])=[O:3])[CH2:7][C@H:8]([C:13]([O:15][CH3:16])=[O:14])[CH2:9]1

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 516892Sodium BicarbonateHCID 86642383methyl (1R*,3R*,4R*)-3-hydroxy-4-methoxycyclopentanecarboxylate

Product 1

HCID 66753156methyl (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentanecarboxylate

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Procedure

To an acetic anhydride (10 mL) solution of nitric acid (5.0 mL, 78 mmol) at 0° C. was added methyl (1R*,3R*,4R*)-3-hydroxy-4-methoxycyclopentanecarboxylate (1.0 g, 5.7 mmol). After 2 hours, the reaction mixture was slowly added to a saturated solution of sodium hydrogen carbonate solution. The aqueous layer was extracted with ethyl acetate (3×100 mL), and the combined organic extracts were washed with brine, dried (magnesium sulfate), and concentrated in vacuo to afford the crude product. The residue was purified by column chromatography on silica gel, eluting with 5/95→25/75 ethyl acetate/hexanes to afford the title compound as a colorless liquid. 1H NMR (500 MHz, CDCl3) δ 1.98-2.10 (m, 2H), 2.36 (ddd, J=6.3, 8.7, 13.9 Hz, 1H), 2.51 (ddd, J=6.5, 8.9, 15.2 Hz, 1H), 2.97 (quintet, J=8.5 Hz, 1H), 3.37 (s, 3H), 3.71 (s, 3H), 3.80-3.85 (m, 1H), 5.28 (td, J=2.4, 6.5 Hz, 1H). Chromatography of the racemic mixture over Chiralcel OD column, eluting with isopropanol/heptane, afforded the separate enantiomers, with the (1S,3R,4R)-stereoisomer as the faster eluting peak and the (1R,3S,4S)-stereoisomer as the slower eluting peak.

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
  2. washthe combined organic extracts were washed with brine
  3. dry with materialdried (magnesium sulfate)
  4. concentrationconcentrated in vacuo
  5. customto afford the crude product
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with 5/95→25/75 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-2eba74f8906547e887c67d560c5d1fdc
Source dataset
uspto-grants-2012_10
Patent number
US08293777B2

Reaction notes

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