반응 #640627

반응 방정식

hydrochloric acid

lithium hydroxide

Lithium hydroxide monohydrate

Ethyl (1R,2S)-1-(tert-butoxycarbonylamino)-2-vinyl-cyclopropane-1-carboxylate

→

(1R,2R)-1-(tert-butoxycarbonylamino)-2-vinyl-cyclopropane-1-carboxylic acid

수율 131.5%

용매

—

ice water

water

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.ADDITIONadded slowly to the mixture
2. 2
   workup.ADDITIONwas added
3. 3
   workup.STIRRINGstirred at room temperature for 2 days
4. 4
   추출then extracted with ethyl acetate (4×900 mL)
5. 5
   세척washed with brine (600 mL)
6. 6
   건조dried over sodium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated to dryness
9. 9
   workup.ADDITIONCyclohexane (100 mL) was added to the
10. 10
    기타dried crude material
11. 11
    농축concentrated

실험 절차

Ethyl (1R,2S)-1-(tert-butoxycarbonylamino)-2-vinyl-cyclopropane-1-carboxylate (61 g, 0.239 mol, 1.0 eq.) and tetrahydrofuran (700 mL) were charged into a 2 L round bottom flask placed in ice/water bath. Lithium hydroxide monohydrate (30 g, 0.714 mol, 3.0 eq.) was dissolved in water (800 mL) and added slowly to the mixture. The reaction mixture was heated at 50° C. for 18 hours. Monitoring the reaction conversion by LCMS showed some residual starting material so lithium hydroxide (20 g, 0.476 mol, 2 eq.) was added. The reaction was stirred further for 5 hours and then stirred at room temperature for 2 days. Monitoring the reaction conversion by LCMS showed complete conversion. The reaction mixture was acidified to pH 3 by slow addition of 1M hydrochloric acid then extracted with ethyl acetate (4×900 mL). The organic extracts were pooled, washed with brine (600 mL), dried over sodium sulfate, filtered and concentrated to dryness. Cyclohexane (100 mL) was added to the dried crude material and concentrated to afford 71.44 g (54.0 g, 100%, corrected for residual solvent) of (1R,2R)-1-(tert-butoxycarbonylamino)-2-vinyl-cyclopropane-1-carboxylic acid as a pale yellow solid which contained residual cyclohexane (24.5% w/was calculated from 1H NMR). The compound was used in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ ppm 5.79 (dt, J=17.01, 9.65 Hz, 1 H), 5.27 (br. s, 1 H), 5.30 (d, J=17.09 Hz, 1 H), 5.14 (d, J=10.38 Hz, 1 H), 2.20 (q, J=8.85 Hz, 1 H), 1.70-1.90 (m, 1 H), 1.52-1.63 (m, 1 H), 1.45 (s, 9 H). LC-MS: purity 100% (UV), tR 1.60 min, m/z [M+Na]+ 250.00.

출처