Water → Ethyl 1-(5-bromopyrimidin-2-yl)-4-hydroxypiperidine-4-carboxylate

HRID 712251ノート

反応式

HRID 712251 の反応式
[OH:1][C:2]1([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[Br:22][C:23]1[CH:24]=[N:25][C:26](Cl)=[N:27][CH:28]=1.O>CCO>[Br:22][C:23]1[CH:24]=[N:25][C:26]([N:5]2[CH2:4][CH2:3][C:2]([OH:1])([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:7][CH2:6]2)=[N:27][CH:28]=1

参加物

6

反応物 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 22717992Ethyl 4-hydroxypiperidine-4-carboxylate

生成物 1

HCID 66977187Ethyl 1-(5-bromopyrimidin-2-yl)-4-hydroxypiperidine-4-carboxylate収率 88%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
80 °C

実験手順

To an ice-cold solution of ethyl 4-hydroxypiperidine-4-carboxylate (0.60 g, 3.44 mmol) in EtOH (15 mL) was added DIPEA (2.95 mL, 17.24 mmol) followed by the addition of 5-bromo-2-chloropyrimidine (0.67 g, 3.44 mmol). The reaction was heated to 80° C. for 3 h then cooled to rt, water added and extracted with EtOAc (3×100 mL). The combined organics were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 20% EtOAc:hexane to obtain the desired product as a yellow solid (0.57 g, 88%). 1H NMR (DMSO-d6): δ 8.44 (s, 2H), 5.58 (s, 1H), 4.27 (m, 2H), 4.10 (q, J=7.20 Hz, 2H), 3.28 (m, 2H), 1.81 (m, 2H), 1.66 (m, 2H), and 1.18 (t, J=7.20 Hz, 3H).

後処理

  1. temperaturethen cooled to rt
  2. extractionextracted with EtOAc (3×100 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude residue was purified over 100-200 M silica-gel

出典と根拠

ORDレコード
ord-c2f19afd2a434dbaac033258eb3efcdd
出典データセット
uspto-grants-2015_11
特許番号
US09181234B2

反応ノート

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