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

HRID 409508

反応式

HRID 409508 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 3776Isopropanol溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-40f2b47bc6584c4181c5aa2428db7676
出典データセット
uspto-grants-2014_06
特許番号
US08759390B2

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