Reaktion #161948

Reaktionsgleichung

#99

ethyl (acetylamino)(bicyclo[4.2.0]octa-1,3,5-trien-7-yl)cyanoacetate

sodium hydroxide

→

(acetylamino)(bicyclo[4.2.0]octa-1,3,5-trien-7-yl)acetic acid

Lösungsmittel

methanol

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was heated
2. 2
   Temperaturat reflux overnight
3. 3
   Einengenconcentrated in vacuo
4. 4
   workup.ADDITIONdiluted with water (40 mL)
5. 5
   ExtraktionThe aqueous layer was extracted with dichloromethane (3×30 mL)
6. 6
   TrocknenThe combined organic layers were dried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated in vacuo
9. 9
   SonstigeThe resulting oil was purified by silica gel chromatography (Solvent A: dichloromethane; Solvent B: 20% methanol in dichloromethane containing 0.02% trifluoroacetic acid; Gradient: 0% to 40% B)
10. 10
    SonstigeThe second eluting peak was isolated
11. 11
    Sonstigeto give #100 (600 mg, 17% over two steps) as a single enantiomer (retention time=3.37 minutes, purity >99%)

Vorschrift

To a mixture of #99 (4.38 mg, <16.1 mmol, 1 eq.) in methanol (30 mL, 0.53 M) was added a 1 N aqueous solution of sodium hydroxide (38 mL, 38 mmol, 2.4 eq.). The reaction mixture was heated at reflux overnight, then concentrated in vacuo, diluted with water (40 mL), and acidified with a 1 N aqueous solution of hydrochloric acid (40 mL). The aqueous layer was extracted with dichloromethane (3×30 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting oil was purified by silica gel chromatography (Solvent A: dichloromethane; Solvent B: 20% methanol in dichloromethane containing 0.02% trifluoroacetic acid; Gradient: 0% to 40% B) then by supercritical fluid chromatography (Column: Chiralpak AD-H, 250×21 mm; Eluent: 85:15 carbon dioxide/methanol; Flow Rate: 65 g/min; Detection: 210 nm; Instrument: Berger minigram preparative SFC system). The second eluting peak was isolated to give #100 (600 mg, 17% over two steps) as a single enantiomer (retention time=3.37 minutes, purity >99%). LC-MS: m/z 220.3 [M+H+], retention time=2.10 minutes; 1H NMR (400 MHz, CD3OD) δ 7.14-7.24 (m, 2H), 7.03-7.09 (m, 2H), 4.59 (d, J=8.6 Hz, 1H), 3.87 (ddd, J=8.5, 5.3, 2.4 Hz, 1H), 3.35 (dd, J=14.5, 5.4 Hz, 1H, assumed; partially obscured by solvent peak), 3.10 (dd, J=14.4, 2.4 Hz, 1H), 2.00 (s, 3H). Optical rotation: [α]D25+70.9° (c 0.67, methanol)

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