Formic Acid → HCID 89666883, compound

HRID 2171271Notes

Reaction equation

HRID 2171271 reaction equation
[CH:1]([OH:3])=[O:2].C([N:11](CC1C=CC=CC=1)[C@@H:12]([CH3:20])[C@H:13]([CH:15]1[CH2:17][C:16]1([CH3:19])[CH3:18])[OH:14])C1C=CC=CC=1>[Pd].C(O)C>[CH3:19][C:16]1([CH3:18])[CH2:17][CH:15]1[CH:13]([OH:14])[C@@H:12]([NH:11][C:1](=[O:3])[O:2][C:15]([CH3:17])([CH3:16])[CH3:13])[CH3:20]

Participants

5

Reactant 2

HCID 284Formic AcidHCID 117643065HCID 117643065, compound

Product 1

HCID 89666883HCID 89666883, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

Formic acid (2.4 ml) and 10% Pd/C (0.4 g) were added to an ethanol solution (60 ml) containing (1S,2S)-2-(dibenzylamino)-1-(2,2-dimethylcyclopropyl)propan-1-ol (2.4 g) obtained in the 5th step, followed by stirring at 90° C. for 5 hours. The reaction solution was filtered through Celite and the filtrate was distilled away under reduced pressure. Diisopropyl ethylamine (1.5 ml) and di-tert-butyl carbonate (1.75 g) were added to a THF (5 ml) solution containing the obtained residue, followed by stirring at room temperature for 40 minutes. Water and a 10% citric acid aqueous solution were added to the reaction solution, followed by extraction with ethyl acetate. The organic layers were washed with water and saturated saline and dried over anhydrous sodium sulfate. Then, the solvent was distilled away under reduced pressure and the obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0 to 1:0.2). A yellow liquid of tert-butyl ((2S)-1-(2,2-dimethylcyclopropyl)-1-hydroxypropan-2-yl)carbamate (0.45 g) was thus obtained.

Workup

  1. customobtained in the 5th step
  2. filtrationThe reaction solution was filtered through Celite
  3. distillationthe filtrate was distilled away under reduced pressure
  4. additionDiisopropyl ethylamine (1.5 ml) and di-tert-butyl carbonate (1.75 g) were added to a THF (5 ml) solution
  5. additioncontaining the obtained residue
  6. stirringby stirring at room temperature for 40 minutes
  7. additionWater and a 10% citric acid aqueous solution were added to the reaction solution
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe organic layers were washed with water and saturated saline
  10. dry with materialdried over anhydrous sodium sulfate
  11. distillationThen, the solvent was distilled away under reduced pressure
  12. customthe obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0 to 1:0.2)

Sources & evidence

ORD record
ord-48d19fb81720480babdd114b7dd86708
Source dataset
uspto-grants-2015_06
Patent number
US09051310B2

Reaction notes

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