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

HRID 245073

반응식

HRID 245073 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-c02fa6d7240245a68740a379e66b0990
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658693B2

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