4-Methylmorpholine → trans-2-(4-Methyl-cyclohexylcarbamoyl)-cyclopropanecarboxylic acid methyl ester

HRID 501280Notes

Reaction equation

HRID 501280 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:7][C@H:6]1[C:8]([OH:10])=O)=[O:4].[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.CN1CCOCC1.[CH3:40][C@H:41]1[CH2:46][CH2:45][C@H:44]([NH2:47])[CH2:43][CH2:42]1>CN(C=O)C>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:7][C@H:6]1[C:8](=[O:10])[NH:47][CH:44]1[CH2:45][CH2:46][CH:41]([CH3:40])[CH2:42][CH2:43]1)=[O:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 12510972rac-(1R,2R)-2-(methoxycarbonyl)cyclopropane-1-carboxylic acidHCID 178461305HCID 178461305, compound

Product 1

HCID 68456814trans-2-(4-Methyl-cyclohexylcarbamoyl)-cyclopropanecarboxylic acid methyl esterYield 95.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Stir a solution of trans-cyclopropane-1,2-dicarboxylic acid monomethyl ester (Example 3a) (3.0 g, 20.8 mmol) and TOTU (8.5 g, 26 mmol) in DMF (300 mL) at ambient temperature for 20 min at which time add N-methylmorpholine (2.4 mL 22.9 mmol) and trans 4-methylcyclohexylamine 3.06 g, 27.0 mmol). After 3 h, remove the solvent and dissolve the residue in H2O/EtOAc. Extract the aqueous layer 3 more times with EtOAc and combine the extracts. Wash the extract with saturated NaHCO3 solution, brine and dry over MgSO4. Concentrate the solvent to afford the crude product, and purify by column chromatography over silica gel to give 4.76 g (95%) of colorless crystals, m/z=240 (M+H)+.

Workup

  1. customremove the solvent
  2. dissolutiondissolve the residue in H2O/EtOAc
  3. extractionExtract the aqueous layer 3 more times with EtOAc
  4. washWash the
  5. extractionextract with saturated NaHCO3 solution, brine
  6. dry with materialdry over MgSO4
  7. concentrationConcentrate the solvent
  8. customto afford the crude product
  9. custompurify by column chromatography over silica gel

Sources & evidence

ORD record
ord-2b11d0b9d5d3465298f57f1b378e1252
Source dataset
uspto-grants-2010_08
Patent number
US07772252B2

Reaction notes

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