Phosphoric Acid → HCID 131733527, compound

HRID 2283688Notes

Reaction equation

HRID 2283688 reaction equation
C([N:3](CC)CC)C.CS(Cl)(=O)=O.[C:13]([O:17][C:18](=[O:28])[NH:19][C@H:20]([C@@H:25](O)[CH3:26])[CH2:21][O:22][CH2:23][CH3:24])([CH3:16])([CH3:15])[CH3:14].P(=O)(O)(O)O>C1COCC1>[C:13]([O:17][C:18](=[O:28])[NH:19][C@H:20]([C@H:25]([NH2:3])[CH3:26])[CH2:21][O:22][CH2:23][CH3:24])([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 1004Phosphoric AcidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 131733526HCID 131733526, compound

Product 1

HCID 131733527HCID 131733527, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (1.25 mL) and methanesulfonyl chloride (0.457 mL) were added to a solution of tert-butyl((2S,3S)-1-ethoxy-3-hydroxybutan-2-yl)carbamate obtained in the above-described Step 2 (1.06 g) in THF (20 mL), and the reaction solution was stirred at room temperature for 20 minutes. 10% Aqueous phosphoric acid solution was added to the reaction solution. Thereafter, the reaction solution was extracted with ethyl acetate and washed successively with a saturated aqueous sodium bicarbonate solution and a saturated saline solution. After drying over anhydrous sodium sulfate, the solvent was evaporated under vacuum. DMF (10 mL) and tetrabutylammonium azide (2 g) were added to the resultant residue, and the reaction solution was stirred at 70° C. for 2 hours. The reaction solution was returned to room temperature, then diluted with diethyl ether, and washed with water and a saturated saline solution. After drying over anhydrous sodium sulfate, the solvent was evaporated under vacuum. The resultant residue was purified by column chromatography on silica gel (developing solvent:hexane/ethyl acetate), and the solvent was evaporated under vacuum. THF (5 mL) and ethanol (5 mL) were added to the resultant residue, and 10% palladium on carbon (600 mg) was added under nitrogen atmosphere. The reaction solution was stirred under hydrogen atmosphere at room temperature overnight. The insolubles were filtrated, and the solvent was evaporated under vacuum to obtain tert-butyl((2R,3R)-3-amino-1-ethoxybutan-2-yl)carbamate as a colorless oily substance.

Workup

  1. extractionThereafter, the reaction solution was extracted with ethyl acetate
  2. washwashed successively with a saturated aqueous sodium bicarbonate solution
  3. dry with materialAfter drying over anhydrous sodium sulfate
  4. customthe solvent was evaporated under vacuum
  5. additionDMF (10 mL) and tetrabutylammonium azide (2 g) were added to the resultant residue
  6. stirringthe reaction solution was stirred at 70° C. for 2 hours
  7. customwas returned to room temperature
  8. additiondiluted with diethyl ether
  9. washwashed with water
  10. dry with materialAfter drying over anhydrous sodium sulfate
  11. customthe solvent was evaporated under vacuum
  12. customThe resultant residue was purified by column chromatography on silica gel (developing solvent:hexane/ethyl acetate)
  13. customthe solvent was evaporated under vacuum
  14. additionTHF (5 mL) and ethanol (5 mL) were added to the resultant residue, and 10% palladium on carbon (600 mg)
  15. additionwas added under nitrogen atmosphere
  16. stirringThe reaction solution was stirred under hydrogen atmosphere at room temperature overnight
  17. filtrationThe insolubles were filtrated
  18. customthe solvent was evaporated under vacuum

Sources & evidence

ORD record
ord-ae5754787b814e468333f143d7e10181
Source dataset
uspto-grants-2015_09
Patent number
US09145414B2

Reaction notes

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