Benzyl Bromide → 4-(R)-[1-(S)-benzyloxy-3-(3-benzyloxyphenyl)-2-(S)-dibenzylaminopropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20349

반응식

HRID 20349 반응식
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([OH:24])[C@@H:14]([NH2:23])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:26])[CH3:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([O:24][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@@H:14]([N:23]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:26])[CH3:25])=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

8

반응물 3

HCID 7498Benzyl Bromide2회HCID 24758Sodium hydride2회HCID 685597324-(R)-[2-(S)-Amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

생성물 1

HCID 685579764-(R)-[1-(S)-benzyloxy-3-(3-benzyloxyphenyl)-2-(S)-dibenzylaminopropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

시약·촉매·용매 4

HCID 21218Trioctylmethylammonium chloride촉매HCID 74236Tetrabutylammonium Bromide촉매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

Add tricaprylmethylammonium chloride (Aliquat® 336) (4.5 g, 11.2 mmol) and tetrabutylammonium bromide (TBAB) (5.7 g, 15.7 mmol) to a solution of 4-(R)-[2-(S)-amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (16.45 g, crude) in tetrahydrofuran (200 mL). Add portionwise 95% sodium hydride (2.6 g, 90 mmol) and stir for 10 minutes. Add benzyl bromide (13.4 mL, 112.5 mmol) and heat at 60° C. for 40 minutes and concentrate. Add more 95% sodium hydride (5.4 g, 225 mmol) and benzyl bromide (27 mL, 225 mmol) in tetrahydrofuran (−5 mL) and stir overnight at 65° C. Dilute with ethyl acetate, quench with water (300 mL), wash with water, and saturated aqueous sodium chloride. Extract the aqueous washes with ethyl acetate, comvine the organic layers, dry (magnesium sulfate), filter and purify twice (silica gel chromatography, eluting with 5:95 to 10:90 ethyl acetate:hexanes) to give the desired compound as an orange residue (16.01 g, 49%).

후처리

  1. concentrationconcentrate
  2. stirringstir overnight at 65° C
  3. customquench with water (300 mL)
  4. washwash with water, and saturated aqueous sodium chloride
  5. extractionExtract the aqueous washes with ethyl acetate
  6. dry with materialdry (magnesium sulfate)
  7. filtrationfilter
  8. custompurify twice
  9. wash(silica gel chromatography, eluting with 5:95 to 10:90 ethyl acetate:hexanes)

출처 및 근거

ORD 기록
ord-90f47e08bb984cd5a0e1a8455c23aa0d
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745438B2

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