Tetrahydrofuran → (S)-1-(1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl)-3-(2,3-difluorobenzyl)-1-methylurea

HRID 409824노트

반응식

HRID 409824 반응식
[CH:1]1[C:6]([N+:7]([O-])=O)=[CH:5][CH:4]=[C:3]([Cl-]C([O-])=O)C=1.[F:14][C:15]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17][NH2:18].[CH3:24]CN(C(C)C)C(C)C.[Si:33]([O:40]C[C@@H](NC)CC=C)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34].C1C[O:51][CH2:50]C1>>[Si:33]([O:40][CH2:1][C@@H:6]([N:7]([CH3:24])[C:50]([NH:18][CH2:17][C:16]1[CH:19]=[CH:20][CH:21]=[C:22]([F:23])[C:15]=1[F:14])=[O:51])[CH2:5][CH:4]=[CH2:3])([C:36]([CH3:37])([CH3:38])[CH3:39])([CH3:34])[CH3:35]

참가 물질

5

반응물 4

HCID 8028Tetrahydrofuran3회HCID 81531DiisopropylethylamineHCID 27369412,3-DifluorobenzylamineHCID 57947450(S)-1-(tert-butyldimethylsilyloxy)-N-methylpent-4-en-2-amine

생성물 1

HCID 57947466(S)-1-(1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl)-3-(2,3-difluorobenzyl)-1-methylurea수율 49%

실험 절차

To a solution of 4-nitrophenylchloroformate (7.04 g, 34.9 mmol) in THF (100 mL) was added a solution of 2,3-difluorobenzylamine (4.26 mL, 36.4 mmol) and DIEA (13.2 mL, 75.9 mmol) in THF (20 mL). The resulting solution was stirred at RT for 20 min. The reaction solution was added into a solution of (S)-1-(tert-butyldimethylsilyloxy)-N-methylpent-4-en-2-amine (31.9 mmol) in THF (50 mL). The resulting solution was stirred at RT overnight. The solvent was removed and the resulting residue was re-dissolved in EtOAc (500 mL). The organic mixture was washed with NaOH (1 N, 100 mL×3), HCl (0.5 N, 100 mL), saturated NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel column using a mixture of DCM and MeOH to give (S)-1-(1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl)-3-(2,3-difluorobenzyl)-1-methylurea (6.8 g, 49%) as a white solid. LRMS (M+H+) m/z 399.2.

후처리

  1. stirringThe resulting solution was stirred at RT overnight
  2. customThe solvent was removed
  3. dissolutionthe resulting residue was re-dissolved in EtOAc (500 mL)
  4. washThe organic mixture was washed with NaOH (1 N, 100 mL×3), HCl (0.5 N, 100 mL), saturated NaHCO3, and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on silica gel column
  9. additiona mixture of DCM and MeOH

출처 및 근거

ORD 기록
ord-a60174769ae54e8593c81694cbd1e311
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759374B2

반응 노트

불러오는 중…