5-Chloro-2,4-difluorobenzoic acid → 5-Chloro-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoic acid

HRID 1849698ノート

反応式

HRID 1849698 の反応式
[F:1][C:2]12[CH2:12][C:6]3([F:13])[CH2:7][C:8]([F:11])([CH2:10][C:4]([CH2:14][OH:15])([CH2:5]3)[CH2:3]1)[CH2:9]2.CC(C)([O-])C.[K+].[Cl:22][C:23]1[C:24](F)=[CH:25][C:26]([F:32])=[C:27]([CH:31]=1)[C:28]([OH:30])=[O:29]>CS(C)=O.C(OCC)(=O)C.O.Cl>[Cl:22][C:23]1[C:24]([O:15][CH2:14][C:4]23[CH2:10][C:8]4([F:11])[CH2:9][C:2]([F:1])([CH2:12][C:6]([F:13])([CH2:7]4)[CH2:5]2)[CH2:3]3)=[CH:25][C:26]([F:32])=[C:27]([CH:31]=1)[C:28]([OH:30])=[O:29]

参加物

8

反応物 3

HCID 148764175-Chloro-2,4-difluorobenzoic acidHCID 23665647Potassium tert-butoxide2 回HCID 57406555(3,5,7-Trifluoroadamantan-1-yl)methanol

生成物 1

HCID 867035705-Chloro-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoic acid収率 40.1%

試薬・触媒・溶媒 4

HCID 313Hydrochloric Acid溶媒HCID 679Dimethyl Sulfoxide溶媒2 回HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of (3,5,7-trifluoroadamantan-1-yl)methanol (1.37 g, 6.22 mmol) and potassium tert-butoxide (0.91 g, 8.09 mmol) in anhydrous dimethylsulfoxide (20 mL) was stirred under nitrogen for 20 minutes. The reaction mixture was treated with a mixture of 5-chloro-2,4-difluorobenzoic acid (1.20 g, 6.22 mmol) and potassium tert-butoxide (0.70 g, 6.22 mmol) in anhydrous dimethylsulfoxide (10 mL) that had been stirred for 10 min. The resulting mixture was stirred under nitrogen at ambient temperature for 20 hours, diluted with ethyl acetate (120 mL), water (20 mL) and 1 M aqueous hydrochloric acid solution (50 mL). The separated organic layer was washed with 1 M aqueous hydrochloric acid solution (50 mL) and brine; dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (2:1 hexanes:ethyl acetate (+0.2% acetic acid v/v)) to provide the title compound (0.98 g, 40%): 1H NMR (300 MHz, DMSO-d6) δ 13.13 (br s, 1H), 7.83 (d, J=7.6 Hz, 1H), 7.18 (d, J=12.6 Hz, 1H), 4.00 (s, 2H), 2.25-2.14 (m, 3H), 2.06-1.96 (m, 3H), 1.81-1.73 (m, 6H); MS (ES−) m/z 391.2, 393.2 (M−1).

後処理

  1. stirringhad been stirred for 10 min
  2. stirringThe resulting mixture was stirred under nitrogen at ambient temperature for 20 hours
  3. washThe separated organic layer was washed with 1 M aqueous hydrochloric acid solution (50 mL) and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (2:1 hexanes

出典と根拠

ORDレコード
ord-2cd9527a4af84d8180109aae0ff44fe8
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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