Cyclohexylamine → (2S,5R)-6-(Benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid

HRID 925137Notes

Reaction equation

HRID 925137 reaction equation
[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([O:20]CC=C)=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C(CCCC)C([O-])=O)C.[Na+].C1(N)CCCCC1>ClCCl.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([OH:20])=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 7965CyclohexylamineHCID 23672331Sodium 2-ethylhexanoateHCID 57389437HCID 57389437, compound

Product 1

HCID 57389355(2S,5R)-6-(Benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acidYield 77.9%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent3×HCID 178418397HCID 178418397, compoundSolvent

Procedure

To a solution of 100 mg (0.316 mmol) of (2S,5R)-allyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate in dichloromethane (2 mL) were added a solution of 0.5M sodium 2-ethylhexanoate in ethyl acetate (1 mL) and 12 mg of tetrakis(triphenylphosphine)palladium(0), followed by stirring at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, followed by liquid separation with saturated aqueous sodium dihydrogen phosphate solution, the aqueous layer was extracted twice with ethyl acetate, and the combined organic layer was dried over anhydrous sodium sulfate. The residue resulting from concentration of the solvent under reduced pressure was dissolved in ethyl acetate, followed by addition of cyclohexylamine (33 mg), and the deposited solid was filtered off, and washed with ether. The resulting solid was dissolved in saturated aqueous sodium dihydrogen phosphate solution, followed by extraction with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. Subsequently, the solvent was concentrated under reduced pressure to afford 68 mg of the title compound as a colorless foamy solid (yield 75%). Instrumental data were consistent with those of the compound of Example 9.

Workup

  1. customfollowed by liquid separation with saturated aqueous sodium dihydrogen phosphate solution
  2. extractionthe aqueous layer was extracted twice with ethyl acetate
  3. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  4. customThe residue resulting from concentration of the solvent under reduced pressure
  5. filtrationthe deposited solid was filtered off
  6. washwashed with ether
  7. dissolutionThe resulting solid was dissolved in saturated aqueous sodium dihydrogen phosphate solution
  8. extractionfollowed by extraction with ethyl acetate
  9. washthe organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationSubsequently, the solvent was concentrated under reduced pressure

Sources & evidence

ORD record
ord-5bbf9731944b42f8bb9c81f458a92367
Source dataset
uspto-grants-2016_03
Patent number
US09284273B2

Reaction notes

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