Dicyclohexylcarbodiimide → HCID 57634048, compound

HRID 2109783Notes

Reaction equation

HRID 2109783 reaction equation
[CH2:1]([N:8]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)[C:10]([OH:12])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:32][NH:33][O:34][CH3:35].N1C2C(=NC=CC=2)N(O)N=1.C1(N=C=NC2CCCCC2)CCCCC1>CCOCC.CCCCCC.CN(C=O)C>[CH2:1]([N:8]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:22])([F:21])[F:23])=[CH:16][CH:15]=1)[C:10]([N:33]([O:34][CH3:35])[CH3:32])=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 181649HOAtHCID 67089327HCID 67089327, compound

Product 1

HCID 57634048HCID 57634048, compoundYield 67.3%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

To a 250 mL round bottom flask was added crude (S)-2-(dibenzylamino)-3-(4-(trifluoromethyl)phenyl)propanoic acid, DMF (700 mL), N,O-dimethylhydroxylamine hydrochloride (25.3 g, 259 mmol), TEA (36.0 mL, 259 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (17.6 g, 130 mmol), and 1,3-dicyclohexylcarbodiimide (26.7 g, 130 mmol) at 0° C. The mixture was allowed to warm to room temperature. After 18 hours, the mixture was diluted with 1 L ether, and the precipitate was filtered through a coarse scintered glass funnel washing with ether. The filtrate was washed with brine (4×200 mL) and the organic layer was again passed through a coarse scintered glass funnel. The aqueous layer was extracted with ether (200 mL), and the combined ether layers were washed with brine (100 mL) and passed through a coarse scintered glass funnel. The organic layers were dried over sodium sulfate and evaporated providing a cloudy yellow oil. The oil was passed through a medium scintered glass funnel washing with ether, and the filtrate was evaporated to provide a clear yellow oil. The crude product was loaded onto a 1.5 kg silica gel column in hexane and eluted at 400 mL/minute 0% to 70% EtOAc in hexane to provide (S)-2-(dibenzylamino)-N-methoxy-N-methyl-3-(4-(trifluoromethyl)phenyl)propanamide (26.52 g, 67.3% yield) as a light yellow oil. LCMS (ES+) m/z=457.3 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.50 (dt, J=3.67, 1.79 Hz, 3H) 3.09-3.19 (m, 3H) 3.31 (s, 3H) 3.68-3.76 (m, 2H) 3.77-3.85 (m, 2H) 7.16-7.34 (m, 12H) 7.63 (d, J=8.22 Hz, 2H).

Workup

  1. filtrationthe precipitate was filtered through a coarse scintered glass funnel
  2. washwashing with ether
  3. washThe filtrate was washed with brine (4×200 mL)
  4. extractionThe aqueous layer was extracted with ether (200 mL)
  5. washthe combined ether layers were washed with brine (100 mL)
  6. dry with materialThe organic layers were dried over sodium sulfate
  7. customevaporated
  8. customproviding a cloudy yellow oil
  9. washwashing with ether
  10. customthe filtrate was evaporated
  11. customto provide a clear yellow oil
  12. washeluted at 400 mL/minute 0% to 70% EtOAc in hexane

Sources & evidence

ORD record
ord-12f81f38004e41e4ad82f2ed18b69c04
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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