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

HRID 20349

Reaction equation

HRID 20349 reaction equation
[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]

Participants

8

Reactant 3

HCID 7498Benzyl Bromide2×HCID 24758Sodium hydride2×HCID 685597324-(R)-[2-(S)-Amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Product 1

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

Reagents, catalysts & solvents 4

HCID 21218Trioctylmethylammonium chlorideCatalystHCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-90f47e08bb984cd5a0e1a8455c23aa0d
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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