Acetic Acid → 2-(3,5-dichloropyridin-4-yl)-N-((5-methyltetrahydrofuran-2-yl)methyl)-2-((triethylsilyl)oxy)ethanamine

HRID 2202693ノート

反応式

HRID 2202693 の反応式
[CH3:1][CH:2]1[O:6][CH:5]([CH2:7]O)[CH2:4][CH2:3]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[Cl:31][C:32]1[CH:33]=[N:34][CH:35]=[C:36]([Cl:49])[C:37]=1[CH:38]([O:41][Si:42]([CH2:47][CH3:48])([CH2:45][CH3:46])[CH2:43][CH3:44])[CH2:39][NH2:40].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Cl:31][C:32]1[CH:33]=[N:34][CH:35]=[C:36]([Cl:49])[C:37]=1[CH:38]([O:41][Si:42]([CH2:45][CH3:46])([CH2:47][CH3:48])[CH2:43][CH3:44])[CH2:39][NH:40][CH2:7][CH:5]1[CH2:4][CH2:3][CH:2]([CH3:1])[O:6]1

参加物

7

反応物 5

HCID 176Acetic AcidHCID 41171Tetrahydro-5-methylfuran-2-methanolHCID 159087TriacetoxyperiodinaneHCID 5049666Sodium triacetoxyborohydrideHCID 1236836992-(3,5-Dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethanamine

生成物 1

HCID 1233887052-(3,5-dichloropyridin-4-yl)-N-((5-methyltetrahydrofuran-2-yl)methyl)-2-((triethylsilyl)oxy)ethanamine

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a clear solution of 5-methyltetrahydrofuran-2-methanol in DCM was added Dess-Martin periodinane (1.2 eq.). The mixture was stirred at room temperature overnight. The crude mixture was directly added to a solution of 2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethanamine (1 eq.) in DCM followed by AcOH (1.2 eq.) and NaBH(OAc)3 (1.5 eq.). The reaction mixture was stirred at room temperature. After 2 h, the mixture was quenched with saturated aqueous Na2S2O3 and saturated NaHCO3. The reaction mixture was extracted with DCM. The organic extract was dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material. The crude material was absorbed onto a plug of silica gel and purified by silica gel column chromatography eluting with a gradient of 0% to 25% EtOAc in heptane to provide 2-(3,5-dichloropyridin-4-yl)-N-((5-methyltetrahydrofuran-2-yl)methyl)-2-((triethylsilyl)oxy)ethanamine (A281) as a light-yellow syrup. 1H NMR (300 MHz, DMSO-d6) δ 8.58 (2H, s), 5.34-5.46 (1H, m), 3.71-3.90 (2H, m), 3.10 (1H, dt, J=12.5, 8.1 Hz), 2.90 (1H, td, J=12.1, 6.0 Hz), 2.52-2.67 (2H, m), 1.71-2.07 (3H, m), 1.47-1.64 (1H, m), 1.19-1.38 (1H, m), 1.11 (3H, t, J=6.3 Hz), 0.77-0.89 (9H, m), 0.40-0.62 (6H, m); LCMS (ESI) m/z 419.1 (M+H)+.

後処理

  1. stirringThe reaction mixture was stirred at room temperature
  2. waitAfter 2 h
  3. customthe mixture was quenched with saturated aqueous Na2S2O3 and saturated NaHCO3
  4. extractionThe reaction mixture was extracted with DCM
  5. extractionThe organic extract
  6. dry with materialwas dried over Na2SO4
  7. filtrationThe solution was filtered
  8. concentrationconcentrated in vacuo
  9. customto give the crude material
  10. customThe crude material was absorbed onto a plug of silica gel
  11. custompurified by silica gel column chromatography
  12. washeluting with a gradient of 0% to 25% EtOAc in heptane

出典と根拠

ORDレコード
ord-7b49aefb9a10494880b392d32ae74d64
出典データセット
uspto-grants-2016_06
特許番号
US09365522B2

反応ノート

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