Diethyl Ether → HCID 86685863, compound

HRID 1629773Notes

Reaction equation

HRID 1629773 reaction equation
CON(C)[C:4](=[O:22])/[CH:5]=[C:6](/[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[CH:10][CH:9]=1)\[CH3:7].[C:24]1([CH3:32])[CH:29]=[CH:28][C:27]([Mg]Br)=[CH:26][CH:25]=1.CCOCC.[NH4+].[Cl-]>C1COCC1.O>[C:24]1([CH3:32])[CH:29]=[CH:28][C:27]([C:4](=[O:22])/[CH:5]=[C:6](/[C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([F:19])([F:20])[F:21])=[CH:12][CH:13]=2)\[CH3:7])=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 86685862HCID 86685862, compoundHCID 178418370HCID 178418370, compound

Product 1

HCID 86685863HCID 86685863, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of Intermediate 11C (1.62 g, 4.89 mmol) in anhydrous THF (25 mL) at −78° C. was added dropwise 0.5 M p-tolylmagnesium bromide in ether (25 mL, 12.5 mmol). The reaction was stirred at −78° C. for 40 min, then gradually warmed to rt. The reaction was poured into 1:1 sat'd aq NH4Cl and water (60 mL). The mixture was extracted with EtOAc. The organic layer was washed with sat'd aq NaCl, dried over MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography (eluted with EtOAc in hexanes) to provide Intermediate 11D (1.34 g, 76%) as a light brown solid. LCMS Anal. Calc'd for C21H21F3O2 362.39, found [M+H] 363.2. 1H NMR (500 MHz, CDCl3) δ 2.01-2.11 (m, 2H), 2.29-2.37 (m, 2H), 2.42 (s, 3H), 2.58 (s, 3H), 4.07 (t, J=6.05 Hz, 2H), 6.92 (d, J=8.80 Hz, 2H), 7.14 (s, 1H), 7.23-7.34 (m, J=8.25 Hz, 2H), 7.55 (d, J=8.80 Hz, 2H), 7.90 (d, J=8.25 Hz, 2H).

Workup

  1. temperaturegradually warmed to rt
  2. extractionThe mixture was extracted with EtOAc
  3. washThe organic layer was washed with sat'd aq NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (eluted with EtOAc in hexanes)

Sources & evidence

ORD record
ord-b860ccbb86074e6486ddfb7b6d606400
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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