Diethyl Ether → HCID 57633950, compound

HRID 2109781Notes

Reaction equation

HRID 2109781 reaction equation
[CH2:1]([N:8]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:9]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1)[C:10](N(OC)C)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][Mg]Br.CCOCC>C1COCC1>[CH2:27]([N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C@@H:9]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=1)[C:10](=[O:11])[CH3:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 57634048HCID 57634048, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 57633950HCID 57633950, compoundYield 85.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a 250 mL round bottom flask containing (S)-2-(dibenzylamino)-N-methoxy-N-methyl-3-(4-(trifluoromethyl)phenyl)propanamide (10.49 g, 23.0 mmol) was added THF (200 mL), and the flask was cooled to 0° C. Methylmagnesium bromide (3.16 M in ether, 12.7 mL, 40.2 mmol) was added dropwise over 10 minutes. After 2 hours, additional methylmagnesium bromide, 3.16 in ether (12.7 mL, 40.2 mmol) was added dropwise over 10 minutes. After 1 hour, the mixture was poured into ammonium chloride—ice (200 mL), washed with brine (100 mL), dried over sodium sulfate, and stored at −20° C. for 15 hours. Plate-like crystals formed the next morning. The mixture was decanted from sodium sulfate and evaporated to provide a yellow oil that crystallized in the freezer over the weekend. The solid was triturated with hexane and chilled at −20° C. before filtration. The product was obtained as a white crystalline solid. The yellow filtrate was adsorbed onto silica gel and purified by chromatography through a Redi-Sep® pre-packed silica gel column (330 g), eluting with a gradient of 0% to 70% EtOAc in hexane to provide additional product as an oil that crystallized under hi vacuum. The two lots were combined to provide (S)-3-(dibenzylamino)-4-(4-(trifluoromethyl)phenyl)butan-2-one (8.09 g, 85.6% yield) as a white solid. LCMS (ES+) m/z=412.3 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.13 (s, 3H) 2.93 (dd, J=13.30, 3.52 Hz, 2H) 3.21 (dd, J=13.30, 9.39 Hz, 1H) 3.50-3.60 (m, 3H) 3.82 (d, J=13.69 Hz, 2H) 7.19-7.30 (m, 4H) 7.30-7.35 (m, 8H) 7.46 (d, J=8.02 Hz, 2H).

Workup

  1. waitAfter 1 hour
  2. washwashed with brine (100 mL)
  3. dry with materialdried over sodium sulfate
  4. waitstored at −20° C. for 15 hours
  5. customPlate-like crystals formed the next morning
  6. customThe mixture was decanted from sodium sulfate
  7. customevaporated
  8. customto provide a yellow oil
  9. customthat crystallized in the freezer over the weekend
  10. customThe solid was triturated with hexane
  11. temperaturechilled at −20° C. before filtration
  12. customThe product was obtained as a white crystalline solid
  13. custompurified by chromatography through a Redi-Sep® pre-packed silica gel column (330 g)
  14. washeluting with a gradient of 0% to 70% EtOAc in hexane
  15. customto provide additional product as an oil that
  16. customcrystallized under hi vacuum

Sources & evidence

ORD record
ord-2c3bd837bb604136bbe46a65a67683ad
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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