Sodium Bicarbonate → tert-Butyl-3-{1-[tert-butyl(dimethyl)silyl]-1H-indol-3-yl}-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 987566Notes

Reaction equation

HRID 987566 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH:3]=1.[Li]C(C)(C)C.CCCCC.[C:28]([O:32][C:33]([N:35]1[CH:40]2[CH2:41][CH2:42][CH:36]1[CH2:37][C:38](=[O:43])[CH2:39]2)=[O:34])([CH3:31])([CH3:30])[CH3:29].C([O-])(O)=O.[Na+]>C1COCC1>[C:28]([O:32][C:33]([N:35]1[CH:40]2[CH2:41][CH2:42][CH:36]1[CH2:37][C:38]([C:2]1[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]([Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH:3]=1)([OH:43])[CH2:39]2)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 2794767tert-Butyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 102448751H-Indole, 3-bromo-1-[(1,1-dimethylethyl)dimethylsilyl]-HCID 178446069HCID 178446069, compound

Product 1

HCID 18009178tert-Butyl-3-{1-[tert-butyl(dimethyl)silyl]-1H-indol-3-yl}-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylateYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To 4.8 g (15.5 mmol) 3-bromo-1-(tert-butyl-dimethyl-silanyl)-1H-indole in 60 mL THF at −78° C. is added 19.1 mL (32.5 mmol) of a 1.7M solution of t-BuLi/pentane in drops over 10 min. After stirring at −78° C. for 30 min, 3.48 g (15.5 mmol) 3-oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester in 20 mL THF is added via a cannula over 5 min. After stirring at 23° C. for 3 h, the reaction mixture is poured into sat. aqueous NaHCO3, and extracted with 2×50 mL EtOAc. The combined organics are washed with 1×100 mL H2O, 1×100 mL brine, dried over MgSO4, filtered and evaporated to an orange oil. Flash chromatography on SiO2 gel, eluting with CH2Cl2/EtOAc (80/1 to 20/1), gives 3.74 g (8.2 mmol, a 53% yield) of the title compound as an off-white wax. MS (ES) m/z 457 (MH)+.

Workup

  1. stirringAfter stirring at 23° C. for 3 h
  2. extractionextracted with 2×50 mL EtOAc
  3. washThe combined organics are washed with 1×100 mL H2O, 1×100 mL brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated to an orange oil
  7. washFlash chromatography on SiO2 gel, eluting with CH2Cl2/EtOAc (80/1 to 20/1)
  8. customgives 3.74 g (8.2 mmol

Sources & evidence

ORD record
ord-47a27274d4f243aabe46b23079eec3c2
Source dataset
uspto-grants-2003_10
Patent number
US06632824B2

Reaction notes

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