Imidazole → 2-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethane

HRID 2250959Notes

Reaction equation

HRID 2250959 reaction equation
[Br:1][CH2:2][C@@H:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:7]([NH:19][CH:20]=[O:21])[CH:6]=1)[OH:4].N1C=CN=C1.[Si:27](Cl)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>CN(C)C=O.C(OC(C)C)(=O)C>[CH2:12]([O:11][C:8]1[CH:9]=[CH:10][C:5]([C@@H:3]([O:4][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[CH2:2][Br:1])=[CH:6][C:7]=1[NH:19][CH:20]=[O:21])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 795Imidazole2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 11142645(R)-N-[5-(2-Bromo-1-hydroxyethyl)-2-(phenylmethoxy)phenyl]formamide

Product 1

HCID 574610672-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethaneYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 7915Isopropyl AcetateSolvent

Procedure

(R)-2-Bromo-1-(3-formamido-4-benzyloxyphenyl)ethanol (9.9 g, 28 mmol) was dissolved in dimethylformamide (36 mL). Imidazole (2.3 g, 34 mmol) and tert-butyldimethylsilyl chloride (4.7 g, 31 mmol) were added. The solution was stirred under nitrogen atmosphere for 72 h. Additional imidazole (0.39 g, 5.7 mmol) and tert-butyldimethylsilyl chloride (0.64 g, 4.3 mmol) were added and the reaction was stirred for an additional 20 h. The reaction mixture was then diluted with a mixture of isopropyl acetate (53 mL) and hexanes (27 mL) and transferred to a separatory funnel. The organic layer was washed twice with a mixture of water (27 mL) and saturated aqueous sodium chloride (27 mL) followed by a final wash with saturated aqueous sodium chloride (27 mL). The organic layer was dried over sodium sulfate. Silica gel (23.6 g) and hexanes (27 mL) were added and the suspension was stirred for 10 min. The solids were removed by filtration and the filtrate concentrated under vacuum. The residue was crystallized from hexanes (45 mL) to afford 8.85 g (19 mmol, 68%) of the title compound as a solid. MS m/z: [M+H+] calcd for C22H30NO3SiBr 464.1; found 464.2.

Workup

  1. stirringthe reaction was stirred for an additional 20 h
  2. customtransferred to a separatory funnel
  3. washThe organic layer was washed twice with a mixture of water (27 mL) and saturated aqueous sodium chloride (27 mL)
  4. washa final wash with saturated aqueous sodium chloride (27 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. additionSilica gel (23.6 g) and hexanes (27 mL) were added
  7. stirringthe suspension was stirred for 10 min
  8. customThe solids were removed by filtration
  9. concentrationthe filtrate concentrated under vacuum
  10. customThe residue was crystallized from hexanes (45 mL)

Sources & evidence

ORD record
ord-e1b51da49dbf40c49051a9536947eb66
Source dataset
uspto-grants-2008_01
Patent number
US07317102B2

Reaction notes

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