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

HRID 712251노트

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HRID 712251 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
80 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c2f19afd2a434dbaac033258eb3efcdd
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181234B2

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