Water → rel-2-Chloro-4-[[(1R,2S,3S)-2,3-dihydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile

HRID 245073

反応式

HRID 245073 の反応式
[NH2:1][C@@H:2]1[CH2:6][CH2:5][C@H:4]([O:7][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[C@@:3]1([CH3:26])[OH:25].[Cl:27][C:28]1[C:35]([CH3:36])=[C:34](F)[CH:33]=[CH:32][C:29]=1[C:30]#[N:31].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[Cl:27][C:28]1[C:35]([CH3:36])=[C:34]([NH:1][C@@H:2]2[CH2:6][CH2:5][C@H:4]([OH:7])[C@:3]2([OH:25])[CH3:26])[CH:33]=[CH:32][C:29]=1[C:30]#[N:31]

参加物

6

反応物 4

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 445509712-Chloro-4-fluoro-3-methylbenzonitrileHCID 86693777rel-(1S,2R,5S)-2-Amino-5-(tert-butyl(diphenyl)silyl)oxy-1-methyl-cyclopentanol

生成物 1

HCID 89510197rel-2-Chloro-4-[[(1R,2S,3S)-2,3-dihydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile収率 6.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

The title compound is prepared by essentially following the procedure described in Example 1, using rel-(1S,2R,5 S)-2-amino-5-(tert-butyl(diphenyl)silyl)oxy-1-methyl-cyclopentanol (409 mg, 1.1 mmol, Preparation 43) and 2-chloro-4-fluoro-3-methyl-benzonitrile (142 mg, 0.84 mmol). A 0.2 M solution of the crude product in THF is treated with tetrabutylammonium fluoride (1.3 mL, 1.3 mmol, 1.0 M in THF) and stirred at room temperature for 16 h. The mixture is treated with water, concentrated in vacuo and extracted with EtOAc. The organic extracts are dried over magnesium sulfate, filtered, and concentrated. The resulting material is purified on silica gel (25-100% EtOAc/hexanes) to give the title compound as a pale yellow oil (15 mg, 6%). The relative stereochemistry is determined by NMR studies. 1H-NMR (400 MHz, DMSO-d6) δ 7.47 (d, J=8.8 Hz, 1H), 6.78 (d, J=8.8 Hz, 1H), 5.60-5.57 (m, 1H), 4.98 (d, J=4.2 Hz, 1H), 4.68 (s, 1H), 3.73-3.70 (m, 2H), 2.12 (s, 3H), 2.09-2.09 (m, 2H), 1.69-1.67 (m, 1H), 1.52-1.49 (m, 1H), 1.07 (s, 3H). LC-ES/MS m/z 281 (M+1).

後処理

  1. customThe title compound is prepared
  2. concentrationconcentrated in vacuo
  3. extractionextracted with EtOAc
  4. dry with materialThe organic extracts are dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting material is purified on silica gel (25-100% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-c02fa6d7240245a68740a379e66b0990
出典データセット
uspto-grants-2014_02
特許番号
US08658693B2

関連ノート

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