반응 #161948

반응 방정식

#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

용매

methanol

methanol

반응 조건

후처리

1. 1
   온도The reaction mixture was heated
2. 2
   온도at reflux overnight
3. 3
   농축concentrated in vacuo
4. 4
   workup.ADDITIONdiluted with water (40 mL)
5. 5
   추출The aqueous layer was extracted with dichloromethane (3×30 mL)
6. 6
   건조The combined organic layers were dried over sodium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated in vacuo
9. 9
   기타The 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
    기타The second eluting peak was isolated
11. 11
    기타to give #100 (600 mg, 17% over two steps) as a single enantiomer (retention time=3.37 minutes, purity >99%)

실험 절차

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)

출처