HCID 67315297, compound → HCID 131729012, compound

HRID 1010910Notes

Reaction equation

HRID 1010910 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]1[CH:16]=[CH:15][C:14]([CH:17]([OH:33])[C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[C:23](OCC2C=CC=CC=2)=O)=[CH:13][CH:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2]>O1CCCC1.CO.[OH-].[Pd+2].[OH-]>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:11]1[CH:16]=[CH:15][C:14]([CH:17]([OH:33])[C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[CH3:23])=[CH:13][CH:12]=1)[CH3:10])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 1

HCID 67315297HCID 67315297, compound

Product 1

HCID 131729012HCID 131729012, compoundYield 99.7%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

300 mg of the compound [52-1] was dissolved in a mixed solvent of 6 mL of tetrahydrofuran and 6 mL of methanol, then 100 mg of a carbon catalyst of 20% palladium hydroxide was added thereto, and the mixture was stirred for 2.5 hours at room temperature under hydrogen atmosphere. The catalyst was filtered through celite and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in 6 mL of tetrahydrofuran, then 147 μL of 37% formaldehyde solution and 420 mg of sodium triacetoxyborohydride were added thereto, and the mixture was stirred for 1.5 hours at room temperature. To the reaction solution was added a saturated aqueous solution of sodium hydrogen carbonate, the solution was extracted with a mixed solvent of chloroform and methanol (mixing ratio: 9/1), and the resulting organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. Thereafter, the insolubles were filtered, and the filtrate was concentrated under reduced pressure, to obtain 220 mg of tert-butyl[(1S)-1-(4-{hydroxy[(2R)-1-methylpyrrolidin-2-yl]methyl}phenyl)ethyl]carbamate [54-1] (hereinafter, referred to as the compound [54-1]).

Workup

  1. filtrationThe catalyst was filtered through celite
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. dissolutionThe resulting residue was dissolved in 6 mL of tetrahydrofuran
  4. addition147 μL of 37% formaldehyde solution and 420 mg of sodium triacetoxyborohydride were added
  5. stirringthe mixture was stirred for 1.5 hours at room temperature
  6. additionTo the reaction solution was added a saturated aqueous solution of sodium hydrogen carbonate
  7. extractionthe solution was extracted with a mixed solvent of chloroform and methanol (mixing ratio: 9/1)
  8. washthe resulting organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationThereafter, the insolubles were filtered
  11. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-214ea07af7b6488da430ab7c09618bbd
Source dataset
uspto-grants-2011_07
Patent number
US07977336B2

Reaction notes

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