Tetrahydrofuran → 3,4-Dimethyl-1-[(S)-4-(4-methoxyphenyl)-3-(pyridin-3-yl)butanoyl]-5-phenylimidazolidin-2-one

HRID 1816010노트

반응식

HRID 1816010 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Mg]Br)=[CH:5][CH:4]=1.[CH2:11]1COCC1.[CH3:16][N:17]1[CH:21]([CH3:22])[CH:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:19]([C:29](=[O:38])/[CH:30]=[CH:31]/[C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)[C:18]1=[O:39]>C1COCC1.C1(C)C=CC=CC=1.[Zn+2].[I-].[I-]>[CH3:16][N:17]1[CH:21]([CH3:22])[CH:20]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:19]([C:29](=[O:38])[CH2:30][C@@H:31]([C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)[CH2:11][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:18]1=[O:39]

참가 물질

6

반응물 3

HCID 8028TetrahydrofuranHCID 207756463,4-Dimethyl-1-[(E)-3-(pyridin-3-yl)prop-2-enoyl]-5-phenylimidazolidin-2-oneHCID 178491912HCID 178491912, 화합물

생성물 1

HCID 698129303,4-Dimethyl-1-[(S)-4-(4-methoxyphenyl)-3-(pyridin-3-yl)butanoyl]-5-phenylimidazolidin-2-one수율 80%

시약·촉매·용매 2

HCID 9883512zinc(II)iodide촉매HCID 22635083Tetrahydrofuran toluene용매

실험 절차

A solution of 4-methoxyphenylmagnesium bromide in THF (0.33 M, 495 mL, 163.5 mmole) was added dropwise to a stirred suspension of (4 R, 5 S)-3,4-dimethyl-1-[(E)-3-(pyridin-3-yl)prop-2-enoyl]-5-phenylimidazolidin-2-one (17.53 g, 54.5 mmole), CuBr-DMS complex (14.1 g, 65.4 mmole), and ZnI2 (20.9 g, 65.4 mmole) in THF/toluene (270 mL) at −15° C. After 1 hr the reaction was quenched with 9:1 saturated NH4Cl/conc. NH4OH and the mixture was stirred open to the air for 30 min. The mixture was diluted with H2O and extracted with EtOAc (3×). The combined organic layers were dried over MgSO4 and concentrated. The residue was taken up in methyl tert-butyl ether (MTBE, 200 mL) and stored at −20° C. overnight. The solid was collected, washed with MTBE, and dried in vacuo. This material was recrystallized from 3:1 hexanes/EtOAc to provide the title compound (19.408 g. 80%): 1H NMR (400 MHz, CDCl3) δ 8.72 (br s, 2 H), 7.50 (narrow m, 1H), 7.12-7.35 (m, 4 H), 6.97-7.03 (m, 2 H), 6.94 (d, J=8.6 Hz, 2 H), 6.72 (d, J=8.6 Hz, 2H), 5.11 (d, J=8.4 Hz, 1 H), 3.70-3.90(m, 2 H), 3.70 (s, 3 H). 3.43-3.58 (m, 1 H), 3.03-3.18 (m, 1 H), 2.75-2.95 (m, 2 H), 2.71 (s, 3 H), 0.66 (d, J=6.5 Hz, 3 H); MS (ES) m/e 444 (M+H)+.

후처리

  1. customAfter 1 hr the reaction was quenched with 9:1 saturated NH4Cl/conc
  2. additionThe mixture was diluted with H2O
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. waitstored at −20° C. overnight
  7. customThe solid was collected
  8. washwashed with MTBE
  9. customdried in vacuo
  10. customThis material was recrystallized from 3:1 hexanes/EtOAc

출처 및 근거

ORD 기록
ord-bb76f61acc474912a7847b4e7855d80c
출처 데이터셋
uspto-grants-2005_04
특허 번호
US06881736B1

반응 노트

불러오는 중…