1,4-Dioxaspiro(4.5)decan-8-ol → 4-(1,4-Dioxaspiro[4.5]decan-8-yloxy)-5-chloro-2-fluorobenzoic acid

HRID 1849802ノート

反応式

HRID 1849802 の反応式
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[Cl:18][C:19]1[C:20](F)=[CH:21][C:22]([F:28])=[C:23]([CH:27]=1)[C:24]([OH:26])=[O:25]>CS(C)=O>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:20]3[C:19]([Cl:18])=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[C:22]([F:28])[CH:21]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1

参加物

5

反応物 3

HCID 5673521,4-Dioxaspiro(4.5)decan-8-olHCID 148764175-Chloro-2,4-difluorobenzoic acidHCID 23665647Potassium tert-butoxide

生成物 1

HCID 867036854-(1,4-Dioxaspiro[4.5]decan-8-yloxy)-5-chloro-2-fluorobenzoic acid収率 21%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

To a solution of 1,4-dioxaspiro[4.5]decan-8-ol (12.90 g, 81.50 mmol) in dimethylsulfoxide (800 mL) was added potassium tert-butoxide (21.00 g, 187.00 mmol). The reaction mixture was stirred at ambient temperature for 15 minutes under nitrogen. To this mixture was added 5-chloro-2,4-difluorobenzoic acid (15.70 g, 81.70 mmol). The mixture was stirred at ambient temperature for 3 days, after which it was split into two equal portions. Each portion was diluted with ethyl acetate (700 mL), washed with 1 M hydrochloric acid (700 mL), a 1:1 mixture of 1 M hydrochloric acid and brine (700 mL), and brine (700 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography with a gradient of a solution of 0.2% acetic acid in ethyl acetate and hexanes from 0-50%, to afford the title compound as a light yellow solid (5.66 g, 21%): 1H NMR (300 MHz, CDCl3) δ 9.24 (br s, 1H), 8.01 (d, J=7.7 Hz, 1H), 6.69 (d, J=12.4 Hz, 1H), 4.54-4.51 (m, 1H), 3.97-3.95 (m, 4H), 2.06-1.93 (m, 4H), 1.81-1.74 (m, 1H), 1.70-1.51 (m, 3H); MS (ES−) m/z 329.1, 331.1 (M−1).

後処理

  1. stirringThe mixture was stirred at ambient temperature for 3 days
  2. customafter which it was split into two equal portions
  3. additionEach portion was diluted with ethyl acetate (700 mL)
  4. washwashed with 1 M hydrochloric acid (700 mL)
  5. additiona 1:1 mixture of 1 M hydrochloric acid and brine (700 mL), and brine (700 mL)
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to dryness
  9. customThe residue was purified by column chromatography with a gradient of a solution of 0.2% acetic acid in ethyl acetate and hexanes from 0-50%

出典と根拠

ORDレコード
ord-e555770ff82947b288060cf1e767c993
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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