Cesium carbonate → HCID 68861315, compound

HRID 898881Notes

Reaction equation

HRID 898881 reaction equation
[CH:1]([NH:3][CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([S:13]C(=O)N(C)C)[CH:10]=2)[CH2:5]1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].C([O-])([O-])=O.[Cs+].[Cs+].Br[C:32]([CH3:41])([CH3:40])[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].[BH4-].[Na+]>C1COCC1>[C:36]([O:35][C:33](=[O:34])[C:32]([CH3:41])([S:13][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[CH2:5][CH:4]([NH:3][CH3:1])[CH2:12]2)[CH3:40])([CH3:39])([CH3:38])[CH3:37]

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 90290tert-Butyl 2-bromo-2-methylpropionateHCID 4311764Sodium borohydrideHCID 21226445Aluminium lithium hydrideHCID 59693390HCID 59693390, compound

Product 1

HCID 68861315HCID 68861315, compoundYield 41.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To dimethylthiocarbamic acid S-(2-formylaminoindan-5-yl)ester (0.772 g; 2.9 mmol) in THF (9 mL) under N2 is added a solution of 1.0 M lithium aluminum hydride (9 mL) at 0° C. The reaction is warmed to RT then stirred at reflux for 24 h. The reaction is cooled to 0° C., quenched with H2O, and the solvent removed under reduced pressure. The residue is dissolved in MeOH (4 mL), to which is added Cs2CO3 (0.304 g; 0.93 mmol), tert-butyl 2-bromoisobutyrate (0.311 mL; 1.39 mmol), and NaBH4 (2.0 g; 52.8 mmol). The reaction mixture is stirred for 18 h, the removed under reduced pressure and the residue partitioned between EtOAc and H2O. The layers are separated, the aqueous phase extracted with EtOAc, the organic extracts combined, washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue is purified by flash chromatography (SiO2) eluting with a CH2Cl2-MeOH gradient to afford 0.186 g (20%) of 2-methyl-2-(2-methylaminoindan-5-ylsulfanyl)propionic acid tert-butyl ester as an oil.

Workup

  1. temperatureat reflux for 24 h
  2. temperatureThe reaction is cooled to 0° C.
  3. customquenched with H2O
  4. customthe solvent removed under reduced pressure
  5. dissolutionThe residue is dissolved in MeOH (4 mL), to which
  6. stirringThe reaction mixture is stirred for 18 h
  7. customthe removed under reduced pressure
  8. customthe residue partitioned between EtOAc and H2O
  9. customThe layers are separated
  10. extractionthe aqueous phase extracted with EtOAc
  11. washwashed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. customevaporated under reduced pressure
  15. customThe crude residue is purified by flash chromatography (SiO2)
  16. washeluting with a CH2Cl2-MeOH gradient

Sources & evidence

ORD record
ord-94eabb5105fe48d288c4c4bc313a86fa
Source dataset
uspto-grants-2008_04
Patent number
US07351857B2

Reaction notes

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