Water → HCID 67490915, compound

HRID 1917401Notes

Reaction equation

HRID 1917401 reaction equation
[CH2:1]([O:8][C:9]([O:11]N1C(=O)CCC1=O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:19][C@:20]1([C:35]([OH:37])=[O:36])[CH2:25][CH2:24][CH2:23][O:22][C@@H:21]1[CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C(N(CC)CC)C.O>O1CCCC1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:19][C@:20]1([C:35]([OH:37])=[O:36])[CH2:25][CH2:24][CH2:23][O:22][C@@H:21]1[CH2:26][NH:27][C:28]([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29])=[O:11])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 83172Benzyl succinimido carbonateHCID 67490997HCID 67490997, compound

Product 1

HCID 67490915HCID 67490915, compoundYield 66.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-(Benzyloxycarbonyloxy)succinimide (1.49 g, 5.98 mmol) was added to a solution of (2R*,3R*)-3-amino-2-(tert-butoxycarbonylamino)methyl-3,4,5,6-tetrahydro-2H-pyrane-3-carboxylic acid (1.09 g, 3.99 mmol) and triethylamine (1.11 mL, 7.96 mmol) in tetrahydrofuran (10 mL)/water (10 mL) under ice-cooling, and the mixture was stirred at room temperature for 15 hours. The reaction solution was diluted with ethyl acetate (150 mL) and washed with 1N hydrochloric acid (50 mL). The resulting organic layer was dried over anhydrous sodium sulfate and filtered. Then, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol:chloroform=2:98→5:95) and then dissolved in a 1N sodium hydroxide solution (50 mL) and washed with diethyl ether (2×20 mL) to remove the remaining benzyl alcohol. The resulting aqueous layer was adjusted to pH 1 to 2 with concentrated hydrochloric acid, followed by extraction with dichloromethane (2×80 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and filtered. Then, the solvent was evaporated under reduced pressure to obtain 1.08 g (66%) of the title compound as a white solid.

Workup

  1. temperaturecooling
  2. washwashed with 1N hydrochloric acid (50 mL)
  3. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customThen, the solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (methanol:chloroform=2:98→5:95)
  7. dissolutiondissolved in a 1N sodium hydroxide solution (50 mL)
  8. washwashed with diethyl ether (2×20 mL)
  9. customto remove the remaining benzyl alcohol
  10. extractionfollowed by extraction with dichloromethane (2×80 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customThen, the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-d95623769956442ca4f9630ba3b61214
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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