Phosgene → 6-Chloro-4-hydroxy-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydro-quinazolin-2(1H)-one

HRID 19701

반응식

HRID 19701 반응식
C(N(CC)CC)C.[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16](=[O:21])[C:17]([F:20])([F:19])[F:18].ClC(Cl)(O[C:26](=[O:32])OC(Cl)(Cl)Cl)Cl.C(Cl)(Cl)=O.FC(F)(F)C=O.[F:44][C:45]([F:49])([F:48])[CH2:46][NH2:47]>C(OCC)C>[Cl:15][C:12]1[CH:11]=[C:10]2[C:9](=[CH:14][CH:13]=1)[NH:8][C:26](=[O:32])[N:47]([CH2:46][C:45]([F:49])([F:48])[F:44])[C:16]2([OH:21])[C:17]([F:20])([F:18])[F:19]

참가 물질

8

반응물 6

HCID 6371PhosgeneHCID 8471Triethylamine2회HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 65564TrifluoroacetaldehydeHCID 94429TriphosgeneHCID 109878821-(2-Amino-5-chlorophenyl)-2,2,2-trifluoroethanone

생성물 1

HCID 593466016-Chloro-4-hydroxy-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydro-quinazolin-2(1H)-one

시약·촉매·용매 1

HCID 3283Diethyl Ether용매3회

반응 조건

온도
0 °C

실험 절차

A mixture of triethylamine (1.3 ml, 9.4 mmol) and 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone (2.1 g, 9.4 mmol) in diethyl ether (18 ml) was cooled to 0° C. under nitrogen atmosphere. In a separate round bottom, triphosgene (929 mg, 3.1 mmol) in diethyl ether (11 ml) was cooled to 0° C. To the phosgene mixture at 0° C. was added dropwise the trifluoroethanone mixture. After stirring for 15 minutes, to this reaction was added a mixture of triethylamine (1.3 ml, 9.4 mmol) and trifluoroethylamine in diethyl ether (18 ml). The reaction stirred for two hours at room temperature and then quenched with water (50 ml) and washed with saturated aqueous sodium bicarbonate solution (2×30 ml). The aqueous layer was extracted with ethyl acetate (3×100 ml) and the combined organic extracts were dried over Na2SO4, filtered and concentrated to give crude material which was purified by flash chromatography on silica gel (0-30% ethyl acetate/hexanes). This afforded 6-chloro-4-hydroxy-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 9.22 (s, 1H), 7.58 (s, 1H), 7.39 (dd, J=2.0 and 8.6 Hz, 1H), 6.84 (d, J=8.4 Hz), 4.71 (m, 1H), 4.38 (s, 1H), 4.18 (m, 1H). Exact Mass (Electrospray, M+H): Calc'd, 349.0173; Found, 349.0166.

후처리

  1. additionwas added
  2. stirringThe reaction stirred for two hours at room temperature
  3. customquenched with water (50 ml)
  4. washwashed with saturated aqueous sodium bicarbonate solution (2×30 ml)
  5. extractionThe aqueous layer was extracted with ethyl acetate (3×100 ml)
  6. dry with materialthe combined organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give crude material which
  10. customwas purified by flash chromatography on silica gel (0-30% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-763c4f7fc23b42d19a03fe81f126be5a
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745452B2

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