Sodium hydride → 3-(2-Cyclopropylmethoxyethylidene)-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester

HRID 1191496Notes

Reaction equation

HRID 1191496 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11](=[CH:16][CH2:17][OH:18])[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:22][CH:23]1[CH2:25][CH2:24]1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11](=[CH:16][CH2:17][O:18][CH2:22][CH:23]1[CH2:25][CH2:24]1)[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 689104973-(2-Hydroxyethylidene)-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester

Product 1

HCID 689113073-(2-Cyclopropylmethoxyethylidene)-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl esterYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A reaction flask was charged with 3-(2-hydroxyethylidene)-8-azabicyclo[3.2.1]octane-8-carboxylic acid t-butyl ester (0.380 g, 1.5 mmol) in dry DMF (2 mL) under Argon. NaH (60% in oil, 0.060 g, 1.5 mmol) was added in portions and the mixture was stirred at 50° for 1 h. The mixture was cooled to rt and bromomethylcyclopropane (0.202 g, 1.5 mmol) was added followed by stirring at rt for 20 h under Argon. The reaction mixture was quenched with water and the product extracted into EtOAc. The combined organic phases were dried over Na2SO4, filtered, and concentrated. The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 1:1) to give the title compound (0.115 g, 25%). 1H NMR (CDCl3) δ 5.38-5.32 (m, 1H), 4.36-3.96 (m, 2H), 3.88-3.75 (m, 2H), 3.09 (d, 2H), 2.48-1.66 (m, 6H), 1.48-1.36 (m, 2H), 1.30 (s, 9H), 0.94-0.33 (m, 1H), 0.40-0.33 (m, 2H), 0.05-0.00 (m, 2)

Workup

  1. stirringby stirring at rt for 20 h under Argon
  2. customThe reaction mixture was quenched with water
  3. extractionthe product extracted into EtOAc
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 1:1)

Sources & evidence

ORD record
ord-de14812ad3264b28a3ae02578dbca767
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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