반응 #76130

반응 방정식

tert-butyl 4-[N-[2-acetoxymethyl-7-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

NaOH

water

→

tert-Butyl 4-[N-[7-Chloro-2-hydroxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   기타the solvent was removed in vacuo
2. 2
   workup.ADDITIONthe residue was treated with water (35 ml)
3. 3
   추출the mixture was extracted with ethyl acetate (3×60 ml)
4. 4
   건조dried (Na2SO4)
5. 5
   농축concentrated in vacuo
6. 6
   기타Purification by column chromatography
7. 7
   세척on elution with 50% ethyl acetate in dichloromethane
8. 8
   기타afforded a white solid which
9. 9
   기타was reprecipitated from dichioromethane (minimum amount)/hexanes
10. 10
    여과The solid was collected by filtration
11. 11
    건조dried in vacuo over P2O5 (0.345 g, 80%), mp 109-111° C.

실험 절차

To a solution of tert-butyl 4-[N-[2-acetoxymethyl-7-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate (0.47 g, 0.92 mmol) in tetrahydrofuran (18 ml), was slowly added 1N aqueous NaOH (1.84 ml, 1.84 mmol) followed by water (1.5 ml). The slightly cloudy solution was stirred at room temperature for 1 hour, the solvent was removed in vacuo and the residue was treated with water (35 ml). The pH was adjusted to 4.5 with 1N HCl and the mixture was extracted with ethyl acetate (3×60 ml). The organics were combined, dried (Na2SO4), and concentrated in vacuo. Purification by column chromatography, on elution with 50% ethyl acetate in dichloromethane, afforded a white solid which was reprecipitated from dichioromethane (minimum amount)/hexanes. The solid was collected by filtration and dried in vacuo over P2O5 (0.345 g, 80%), mp 109-111° C.; 1H-NMR (DMSO-d6); 1.49 (s, 9H, CO2But), 3.50 (s, 3H, N3-Me), 3.25 (s (poorly resolved triplet), 1H, C≡CH), 4.40 (s, 2H, CH2C≡C), 4.57 (d, J=5.70 Hz, 2H, 2-CH2OH), 4.80 (s, 2H, 6-CH2), 5.67 (t, J=6.4 Hz, 1H, CH2OH), 6.78 (d, J=8.80 Hz, 2H, 3′,5′-ArH), 7.72 (d, J=8.44 Hz, 2H, 2′,6′-Ar), 7.82, 7.87 (2×s, 2H, 5-H, 8-H); MS (FAB, m/z) 467, 469 (M+, 95%, 45% respectively; Cl isotopic pattern).

출처