Hydrochloric Acid → HCID 86730719, compound

HRID 633845Notes

Reaction equation

HRID 633845 reaction equation
ClC(OCC)=O.[C:7]([O:11][C:12]([NH:14][C@H:15]1[CH2:20][O:19][C@H:18]([C:21]([OH:23])=O)[CH2:17][CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].C(N(C(C)C)CC)(C)C.[N+:33](=[CH2:35])=[N-:34].Cl>O1CCCC1.C(OCC)(=O)C>[C:7]([O:11][C:12](=[O:13])[NH:14][C@@H:15]1[CH2:16][CH2:17][C@@H:18]([C:21](=[O:23])[CH:35]=[N+:33]=[N-:34])[O:19][CH2:20]1)([CH3:8])([CH3:9])[CH3:10]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 9550DiazomethaneHCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 109228122,6-Anhydro-5-[(tert-butoxycarbonyl)amino]-3,4,5-trideoxy-L-erythro-hexonic acid

Product 1

HCID 86730719HCID 86730719, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl chloroformate (605 μL, 6.36 mmol, 1.2 eq) is added dropwise at 0° C. to a stirred solution of (2S,5R)-5-tert-butoxycarbonylamino-tetrahydro-pyran-2-carboxylic acid (1.3 g, 5.30 mmol, 1.0 eq) and diisopropylethylamine (1.38 mL, 7.95 mmol, 1.5 eq) in tetrahydrofuran (50 mL). After 30 minutes stirring at room temperature the reaction mixture is cooled down to −20° C. before the addition of diazomethane (2.0 M solution in diethyl ether, 26.5 mL, 53.0 mmol, 10.0 eq). After 15 hours stirring at −20° C., the reaction mixture is carefully acidified to pH 6 with 1.0 N hydrochloric acid aqueous solution and then extracted with ethyl acetate (3×30 mL). The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 10:1 to 3:1, v/v) to afford (3R,6S)-[6-(2-diazo-acetyl)-tetrahydro-pyran-3-yl]-carbamic acid tert-butyl ester as a white solid (1.14 g, 80% yield).

Workup

  1. stirringAfter 15 hours stirring at −20° C.
  2. extractionextracted with ethyl acetate (3×30 mL)
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product that
  8. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-fafbc4d39ae4435e8efe276b50c2393c
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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