Methyl Acrylate → 6'-(3-Fluoropropoxy)spiro[cyclohexane-1,2'-indene]-1',4(3'H)-dione

HRID 539301ノート

反応式

HRID 539301 の反応式
[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][CH2:11][C:12]2=[O:15])=[CH:8][CH:7]=1.[C:16]([O:20]C)(=O)[CH:17]=[CH2:18].[CH3:22][C:23](C)([O-])C.[K+].[OH-].[K+]>[Cl-].[Na+].O.O>[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11]3([CH2:18][CH2:17][C:16](=[O:20])[CH2:23][CH2:22]3)[C:12]2=[O:15])=[CH:8][CH:7]=1

参加物

7

反応物 4

HCID 7294Methyl AcrylateHCID 14797Potassium HydroxideHCID 23665647Potassium tert-butoxideHCID 679794716-(3-Fluoropropoxy)-indan-1-one2 回

生成物 1

HCID 679795576'-(3-Fluoropropoxy)spiro[cyclohexane-1,2'-indene]-1',4(3'H)-dione収率 66%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
0 °C

実験手順

A mixture of 6-(3-fluoropropoxy)-2,3-dihydro-1H-inden-1-one (Intermediate 62, 3.42 g, 16.4 mmol) and methyl acrylate (3.26 mL, 36.1 mmol) in 2-Me THF (15 mL) was cooled to 0° C. Potassium tert-butoxide (2.21 g, 19.71 mmol) was added in portions. After stirring for 1 h at r.t., water (22.5 mL) and KOH (0.921 g, 16.4 mmol) were added and the mixture was heated at reflux for 4.5 h. The mixture was allowed to cool to r.t. and brine was added. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to yield 3.14 g (66% yield) of the title compound which was used in the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 1.82-1.91 (m, 2 H), 2.13-2.27 (m, 4 H), 2.41-2.52 (m, 2 H), 2.70 (dt, 2 H), 3.16 (s, 2 H), 4.11-4.17 (m, 2 H), 4.60 (t, 1 H), 4.72 (t, 1 H), 7.21-7.27 (m, 2 H), 7.39 (dd, 1 H); MS (ES+) m/z 291 [M+H]+.

後処理

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 4.5 h
  3. temperatureto cool to r.t.
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-c277da5b5c3e4107b37030bc3abb248c
出典データセット
uspto-grants-2014_10
特許番号
US08865911B2

反応ノート

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