Triethylamine → 3-(5-Bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione

HRID 63481

반응식

HRID 63481 반응식
CO[C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[CH:6][C:5]=1[CH2:11]Br.Cl.[NH2:15][CH:16]1[CH2:21][CH2:20][C:19](=[O:22])[NH:18][C:17]1=[O:23].C(N(CC)CC)C>CN(C=O)C>[Br:10][C:7]1[CH:6]=[C:5]2[C:4](=[CH:9][CH:8]=1)[C:3](=[O:13])[N:15]([CH:16]1[CH2:21][CH2:20][C:19](=[O:22])[NH:18][C:17]1=[O:23])[CH2:11]2

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 22031079Methyl 4-bromo-2-(bromomethyl)benzoate

생성물 1

HCID 690490113-(5-Bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione수율 20.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mechanically stirred mixture of 4-bromo-2-bromomethyl-benzoic acid methyl ester (121 g, 390 mmol) and 3-amino-piperidine-2,6-dione hydrochloride (64.2 g, 390 mmol) in DMF (400 mL) was treated dropwise with triethylamine (98.5 g, 980 mmol) over 75 minutes. After the addition was completed, the reaction mixture was stirred at room temperature overnight. The mixture was quenched sequentially with acetic acid (50 mL), water (2500 mL) and a 1:1 mixture of ethyl acetate and hexanes (600 mL). After stirring the mixture for 20 minutes, the solid was filtered, washed with water and air dried overnight. The solid was stirred in acetic acid (200 mL) and refluxed for 2 hours. The mixture was cooled to room temperature and filtered. The solid was washed with additional acetic acid, hexanes and air dried overnight to give 25.4 g of 3-(5-bromo-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione as a grey solid, in 20% yield; 1H NMR (DMSO-d6) δ 1.97-2.04 (m, 1H), 2.32-2.46 (m, 1H), 2.56-2.63 (m, 1H), 2.85-2.97 (m, 1H), 4.34 (d, J=17.7 Hz, 1H), 4.47 (d, J=17.7 Hz, 1H), 5.11 (dd, J=13.2 Hz, J=5.1 Hz, 1H), 7.67 (d, J=8.1 Hz, 1H), 7.72 (dd, J=8.1 Hz, J=1.5 Hz, 1H), 7.89 (d, J=0.9 Hz, 1H), 11.00 (s, 1H).

후처리

  1. additionAfter the addition
  2. customThe mixture was quenched sequentially with acetic acid (50 mL), water (2500 mL)
  3. additiona 1:1 mixture of ethyl acetate and hexanes (600 mL)
  4. stirringAfter stirring the mixture for 20 minutes
  5. filtrationthe solid was filtered
  6. washwashed with water and air
  7. customdried overnight
  8. stirringThe solid was stirred in acetic acid (200 mL)
  9. temperaturerefluxed for 2 hours
  10. temperatureThe mixture was cooled to room temperature
  11. filtrationfiltered
  12. washThe solid was washed with additional acetic acid, hexanes and air
  13. customdried overnight

출처 및 근거

ORD 기록
ord-d380ecd032244e47ba9f40b9e619aca5
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447070B2

연결된 노트

불러오는 중…