Triethylamine → 5-(2-Chloro-phenyl)-3-(tetrahydro-pyran-2-yloxymethyl)-isoxazole-4-carboxylic acid ethyl ester

HRID 349260

반응식

HRID 349260 반응식
[N+:1]([CH2:4][CH2:5][O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][O:8]1)([O-:3])=O.[CH2:13]([O:15][C:16](=[O:26])[C:17]#[C:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25])[CH3:14].C1(N=C=O)C=CC(N=C=O)=CC=1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH2:13]([O:15][C:16]([C:17]1[C:4]([CH2:5][O:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)=[N:1][O:3][C:18]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25])=[O:26])[CH3:14]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 610091,4-DiisocyanatobenzeneHCID 641308Ethyl 3-(2-chlorophenyl)prop-2-ynoateHCID 37486562-(2-Nitroethoxy)tetrahydropyran

생성물 1

HCID 691236215-(2-Chloro-phenyl)-3-(tetrahydro-pyran-2-yloxymethyl)-isoxazole-4-carboxylic acid ethyl ester수율 94.2%

시약·촉매·용매 1

HCID 1140Toluene용매2회

반응 조건

온도
70 °C

실험 절차

Add 2-(2-nitroethoxy)tetrahydropyran (41 mL, 270 mmol) dropwise in toluene (100 mL) to a solution of (2-chloro-phenyl)-propynoic acid ethyl ester (28.3 g, 135 mmol), 1,4-phenylene diisocyanate (67 g, 420 mmol) and triethylamine (15 mL) in toluene (900 mL). Stir at reflux for 10 h. While still warm (˜70° C.), filter the reaction mixture through Celite®, washing the solids with EtOAc. Wash the filtrate with 1N HCl (500 mL) and brine (500 mL). Dry the organics over Na2SO4, filter and concentrate under reduced pressure. Purification by flash chromatography (silica gel, 85:15 Hexanes/EtOAc) gives the title compound (46.5 g, 94%). MS (m/e): 282 (M−C5H8O+H+); 1H NMR (300 MHz, CDCl3) δ 7.35–7.55 (m, 4H), 5.09 (d, J=13 Hz, 1), 4.85–4.91 (m, 2H), 4.15–4.22 (m, 2H), 3.91–4.01 (m, 1H), 3.52–3.61 (m, 1H), 1.49–1.92 (m, 6H), 1.12 (t, J=7 Hz, 3H); TLC Rf=0.53 (7:3 Hexanes/EtOAc).

후처리

  1. temperatureat reflux for 10 h
  2. filtrationfilter the reaction mixture through Celite®
  3. washwashing the solids with EtOAc
  4. washWash the filtrate with 1N HCl (500 mL) and brine (500 mL)
  5. dry with materialDry the organics over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customPurification by flash chromatography (silica gel, 85:15 Hexanes/EtOAc)

출처 및 근거

ORD 기록
ord-341fc749cbda49a795d8b7d91d739698
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07179804B2

연결된 노트

불러오는 중…