Triethylamine → 3-(2-Chloropyrimidin-4-yl)-8-oxa-3-azabicyclo[3,2,1]octane

HRID 75408

反応式

HRID 75408 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.Cl.[CH:10]12[O:17][CH:14]([CH2:15][CH2:16]1)[CH2:13][NH:12][CH2:11]2.CCN(CC)CC>CCO>[Cl:1][C:2]1[N:7]=[C:6]([N:12]2[CH2:11][CH:10]3[O:17][CH:14]([CH2:15][CH2:16]3)[CH2:13]2)[CH:5]=[CH:4][N:3]=1.[Cl:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:12]2[CH2:11][CH:10]3[O:17][CH:14]([CH2:15][CH2:16]3)[CH2:13]2)[N:7]=1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 775312,4-DichloropyrimidineHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochloride

生成物 2

HCID 663715273-(2-Chloropyrimidin-4-yl)-8-oxa-3-azabicyclo[3,2,1]octane収率 89%HCID 866658783-(4-Chloro-pyrimidin-2-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane収率 4%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

A 745 mg (5 mmol) portion 2,4-dichloropyrimidine (1) was dissolved in 20 mL EtOH at 0 C. 8-oxa-3-aza-bicyclo[3.2.1]octane hydrochloride (2, 748 mg, 5 mmol) was added followed by the addition of NEt3 (2.1 mL, 15 mmol). The mixture was stirred for 1 hour at ambient temperature. The mixture was concentrated, dissolved in EtOAc and washed with saturated NaHCO3. The aqueous phase was extracted with EtOAc and the combined organic phases were dried (MgSO4), filtered and concentrated. The mixture was purified by silica gel chromatography (20-70% EtOAc in hexanes) to give 1,003 mg (4.4 mmol, 89%) of 3-(2-chloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (3) along with 50 mg (0.22 mmol, 4%) of 3-(4-chloro-pyrimidin-2-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (4).

後処理

  1. concentrationThe mixture was concentrated
  2. dissolutiondissolved in EtOAc
  3. washwashed with saturated NaHCO3
  4. extractionThe aqueous phase was extracted with EtOAc
  5. dry with materialthe combined organic phases were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe mixture was purified by silica gel chromatography (20-70% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-42bc12a8e8aa4652ad482317cfda17d5
出典データセット
uspto-grants-2014_09
特許番号
US08835429B2

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