1,4-Dibromobutane → trans-(4-Pyrrolidin-1-yl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester

HRID 39421Notes

Reaction equation

HRID 39421 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[C@H:13]([NH2:14])[CH2:12][CH2:11][O:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:23][CH2:24][CH2:25][CH2:26]Br>C(#N)C>[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[C@H:13]([N:14]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:12][CH2:11][O:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 80561,4-DibromobutaneHCID 11430Potassium CarbonateHCID 67358958tert-Butyl ((3S,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate2×

Product 1

HCID 67358972trans-(4-Pyrrolidin-1-yl-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl esterYield 84%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

trans-(4-Amino-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (intermediate G, 330 mg, 1.53 mmol) was dissolved in 8 mL acetonitrile. Potassium carbonate (1.05 g, 7.6 mmol) and 1,4-dibromobutane (672 mg, 3.11 mmol) were added and the reaction mixture was refluxed overnight. The solvent was evaporated off. The residue was taken up in water and extracted three times with diethylether. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 1:0:0→140:10:1) yielded the title compound as a yellow oil (347 mg, 84%), MS: m/e=271.3 [(M+H)+].

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. customThe solvent was evaporated off
  3. extractionextracted three times with diethylether
  4. customThe combined organic phases were dried on sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 1:0:0→140:10:1)

Sources & evidence

ORD record
ord-3fea5b1e26de4ca2a508db93057c2192
Source dataset
uspto-grants-2013_09
Patent number
US08524909B2

Reaction notes

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