Imidazole → N-[2-(benzyloxy)-ethyl]-4-{[tert-butyl(dimethyl)silyl]oxy}butan-1-amine

HRID 2066593Notes

Reaction equation

HRID 2066593 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][NH2:6].[C:7]([Si:11](Cl)([CH3:13])[CH3:12])([CH3:10])([CH3:9])[CH3:8].N1C=CN=C1.[CH2:20]([O:27][CH2:28][CH:29]=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.ClC(Cl)C>[CH2:20]([O:27][CH2:28][CH2:29][NH:6][CH2:5][CH2:4][CH2:3][CH2:2][O:1][Si:11]([C:7]([CH3:10])([CH3:9])[CH3:8])([CH3:13])[CH3:12])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

8

Reactant 5

HCID 795ImidazoleHCID 258684-Amino-1-butanolHCID 28928tert-Butyldimethylsilyl chlorideHCID 108989(Phenylmethoxy)acetaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 66997788N-[2-(benzyloxy)-ethyl]-4-{[tert-butyl(dimethyl)silyl]oxy}butan-1-amine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of 4-hydroxybutylamine (4.0 g, 44.9 mmol), tert-butyldimethyl-silyl chloride (7.4 g, 49.3 mmol) and imidazole (6.7 g, 98.7 mmol) in dichloromethane (150 mL) was stirred at room temperature for 2 hours. The product mixture was washed successively with aqueous NaHCOs, water, and brine. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. This intermediate silylated aminoalcohol was used without further purification. To a mixture of the amine (1.0 g, 4.9 mmol) and benzyloxyacetaldehyde (0.74 g, 4.9 mmol) in dichloroethane (15 mL) at room temperature, sodium triacetoxyborohydride (1.3 g, 6.3 mmol) was added. The reaction mixture was concentrated under vacuum. The residue was partitioned between ethyl acetate and aqueous sodium carbonate. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 2% methanol in dichloromethane. Collection and concentration of appropriate fractions afforded the title silyloxybutyl-amine.

Workup

  1. washThe product mixture was washed successively with aqueous NaHCOs, water, and brine
  2. extractionThe organic extract
  3. dry with materialwas dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThis intermediate silylated aminoalcohol was used without further purification
  7. concentrationThe reaction mixture was concentrated under vacuum
  8. customThe residue was partitioned between ethyl acetate and aqueous sodium carbonate
  9. extractionThe organic extract
  10. dry with materialwas dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under vacuum
  13. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-895a6700f30f44cbbf46e1a5ccfd7155
Source dataset
uspto-grants-2012_10
Patent number
US08293731B2

Reaction notes

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