Toluene → HCID 58017255, compound

HRID 661564Notes

Reaction equation

HRID 661564 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:11][CH2:10][CH:9]2[N:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:6]1[CH2:7][CH2:8]2)=[O:4].I[CH2:21][CH2:22][CH3:23].C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[Cl-].[NH4+]>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1([CH2:21][CH2:22][CH3:23])[CH2:11][CH2:10][CH:9]2[N:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:6]1[CH2:7][CH2:8]2)=[O:4]

Participants

7

Reactant 5

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 336431-IodopropaneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 580172018-(1,1-Dimethylethyl) 2-methyl 8-azabicyclo[3.2.1]octane-2,8-dicarboxylate

Product 1

HCID 58017255HCID 58017255, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-76 °C

Procedure

8-Azabicyclo[3.2.1]octane-2,8-dicarboxylic acid 8-tert-butyl ester 2-methyl ester as a mixture of endo and exo isomers from Step 5 (1.0 g, 3.7 mmol) was dissolved in tetrahydrofuran (30 mL), and 1-iodopropane (3.2 g, 19 mmol) was added. The resulting solution was cooled to −76° C. and treated dropwise over 15 minutes with solution of potassium bis(trimethylsilyl) amide in toluene (0.5 M, 11.1 mL, 5.6 mmol). Stirring was continued at −76° C. for 1.5 hours, and the reaction mixture was then allowed to warm slowly to 0° C. over 3 hours. Saturated aqueous ammonium chloride was added, and the resulting mixture was extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, ethyl acetate/hexane) to provide 2-propyl-8-aza-bicyclo[3.2.1]octane-2,8-dicarboxylic acid 8-tert-butyl ester 2-methyl ester as a mixture of endo and exo isomers as a pale yellow oil (0.99 g, 85% yield).

Workup

  1. temperatureto warm slowly to 0° C. over 3 hours
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe combined organic extracts were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (silica gel, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-101200d0c8224070947ecd4662589f71
Source dataset
uspto-grants-2011_12
Patent number
US08084623B2

Reaction notes

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