4-Methylmorpholine → HCID 86706409, compound

HRID 1396997Notes

Reaction equation

HRID 1396997 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.Cl.[NH:44]1[C@H:48]([C:49]([OH:51])=[O:50])[CH2:47][CH:46]=[N:45]1>C(#N)C>[CH:1]1([CH2:6][C@H:7]([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:8]([N:44]2[C@H:48]([C:49]([OH:51])=[O:50])[CH2:47][CH:46]=[N:45]2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27340604-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-iumHCID 9816539(R)-4-(tert-Butoxy)-2-(cyclopentylmethyl)-4-oxobutanoic acidHCID 131732110HCID 131732110, compound

Product 1

HCID 86706409HCID 86706409, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a 1000 ml round bottom flask under N2 was added (2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoic acid (Tetrahedron, 2001, 57(36), 7675-7683) (38.1 g, 149 mmol) in acetonitrile (650 mL) at 0° C., followed by N-methylmorpholine (82 mL, 744 mmol) and 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium (53.7 g, 164 mmol). The solution was stirred at the same temperature for 2 hours and then (5S)-4,5-dihydro-1H-pyrazole-5-carboxylic acid, hydrochloride (22.4 g, 149 mmol) was added. The solution was allowed to warm up to room temperature and stirring continued overnight. LCMS showed that the reaction was complete. The acetonitrile was removed under reduced pressure, and the residue was taken up in DCM (500 mL) and neutralized by the addition of 2 N HCl. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by Combiflash automated silica gel chromatography (0-5% methanol containing 1% formic acid/DCM) to provide (5S)-1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (27.7 g, 79 mmol, 53% yield) as a clear oil. LCMS: [M+H]+: 353.4.

Workup

  1. stirringstirring continued overnight
  2. customThe acetonitrile was removed under reduced pressure
  3. additionneutralized by the addition of 2 N HCl
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Combiflash automated silica gel chromatography (0-5% methanol containing 1% formic acid/DCM)

Sources & evidence

ORD record
ord-6d2106ab22ce4eefb52d396c777cdf3d
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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