Acetic Acid → Methyl 2-(4-chloro-3-(trifluoromethyl)phenyl)-4-oxochroman-3-carboxylate

HRID 409508

반응식

HRID 409508 반응식
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:14])[CH2:9][C:10]([O:12][CH3:13])=[O:11].[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][C:17]=1[C:24]([F:27])([F:26])[F:25].N1CCCCC1.C(O)(=O)C>C(O)(C)C.O>[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]2[CH:9]([C:10]([O:12][CH3:13])=[O:11])[C:8](=[O:14])[C:3]3[C:2](=[CH:7][CH:6]=[CH:5][CH:4]=3)[O:1]2)=[CH:18][C:17]=1[C:24]([F:25])([F:26])[F:27]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 1186424-Chloro-3-(trifluoromethyl)benzaldehydeHCID 12381316Methyl 3-(2-hydroxyphenyl)-3-oxopropanoate

생성물 1

HCID 67155700Methyl 2-(4-chloro-3-(trifluoromethyl)phenyl)-4-oxochroman-3-carboxylate수율 51.5%

시약·촉매·용매 2

HCID 962Water용매HCID 3776Isopropanol용매

실험 절차

A mixture of methyl 3-(2-hydroxyphenyl)-3-oxopropanoate (prepared according to Cushman, M. et al., J. Med. Chem. 1991, 200 mg, 1.03 mmol) and 4-chloro-3-(trifluoromethyl)benzaldehyde (148 μL, 1.03 mmol) in isopropanol (4.0 mL) was treated with piperidine (10 μL, 103 μmol) and acetic acid (5.9 μL, 103 μmol) and heated to reflux for 16.5 h. After this time, water (2.0 mL) was added and the solution was slowly cooled to rt, whereupon crystals formed. After standing at rt, the mixture was cooled on ice, and the resulting crystals were collected by filtration and dried to provide methyl 2-(4-chloro-3-(trifluoromethyl)phenyl)-4-oxochroman-3-carboxylate as a white crystalline solid (204 mg, 51%). A second crop (47 mg) was obtained from the mother liquor, raising the total yield to 63%. The NMR indicated predominantly the enolic form. 1H NMR (500 MHz, CDCl3) δ ppm 3.79 (s, 3 H) 6.24 (s, 1 H) 6.82 (d, J=8.2 Hz, 1 H) 7.00 (t, J=7.7 Hz, 1 H) 7.31 (t, J=6.9 Hz, 1 H) 7.42 (m, 2 H) 7.70 (m, 2 H) 12.27 (br. s, 1 H). Mass spectrum m/z 407.19, 409.18 (M+Na)+.

후처리

  1. temperatureheated
  2. temperatureto reflux for 16.5 h
  3. customformed
  4. customAfter standing at rt
  5. temperaturethe mixture was cooled on ice
  6. filtrationthe resulting crystals were collected by filtration
  7. customdried

출처 및 근거

ORD 기록
ord-40f2b47bc6584c4181c5aa2428db7676
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759390B2

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