Carbon Dioxide → HCID 178497106, compound

HRID 230022Notes

Reaction equation

HRID 230022 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([NH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]1)[CH2:6][CH2:5]2.C([Li])CCC.[C:27](=[O:29])=[O:28].[CH3:30][Si](C=[N+]=[N-])(C)C>C1(C)C=CC=CC=1.C1COCC1.CO.C(Cl)Cl>[C:18]([C@H:15]1[CH2:16][CH2:17][C@H:12]([NH:11][CH:7]2[C:8]3[C:4](=[CH:3][C:2]([C:27]([O:29][CH3:30])=[O:28])=[CH:10][CH:9]=3)[CH2:5][CH2:6]2)[CH2:13][CH2:14]1)([CH3:21])([CH3:20])[CH3:19]

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 167693TrimethylsilyldiazomethaneHCID 178418339ButyllithiumHCID 178445668HCID 178445668, compound

Product 1

HCID 178497106HCID 178497106, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
-78 °C

Procedure

(5-Bromo-2,3-dihydro-1H-inden-1-yl)(trans-4-tert-butylcyclohexyl)amine (1.20 g, 3.42 mmol) was dried azeotropically from dry THF in toluene (3×) and kept under high vacuum for 2 h before use. It was then dissolved in anhydrous THF (20 mL) and cooled to −78° C. n-Butyl lithium (1.6 M solution in Hexane, 8.40 mL, 13.68 mmol) was added over 15 min. After stirring at −78° C. for 30 min, excess dry ice cubes were then added. The reaction mixture was allowed to warm up slowly and then quenched at −20° C. with saturated aqueous NH4Cl (20 mL). Extractions with EtOAc (3×15 mL), drying (Na2SO4), filtration and removal of solvent gave the crude carboxylic acid. The crude carboxylic acid was dissolved in MeOH/DCM (1:2, 10 mL) and then (trimethylsilyl)diazomethane (2.0 M solution in Hexane) was added until gas bubbling ceased and the yellow color sustained. Concentration and chromatography (35% EtOAc in Hexane) afforded methyl 1-[(trans-4-tert-butylcyclohexyl)amino]indane-5-carboxylate. HPLC/MS: m/z=330.3 (M+1), Rt=2.85 min.

Workup

  1. additionwas added over 15 min
  2. temperatureto warm up slowly
  3. customquenched at −20° C. with saturated aqueous NH4Cl (20 mL)
  4. extractionExtractions with EtOAc (3×15 mL)
  5. customdrying
  6. filtration(Na2SO4), filtration and removal of solvent
  7. customgave the crude carboxylic acid
  8. custombubbling
  9. concentrationConcentration and chromatography (35% EtOAc in Hexane)

Sources & evidence

ORD record
ord-4cd8ce9ee4784c2090da6beb294a5fd8
Source dataset
uspto-grants-2009_07
Patent number
US07563815B2

Reaction notes

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