Diethyl Ether → HCID 86670973, compound

HRID 515345Notes

Reaction equation

HRID 515345 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]([C:9]1[CH:33]=[CH:32][C:12]([CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([C:20]([C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:31])[CH3:30])=[CH:24][CH:23]=3)=[O:21])[CH2:16][CH2:15]2)=[CH:11][CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].[CH3:36][Mg]Br.C(OCC)C>O1CCCC1>[F:35][C:2]([F:1])([F:34])[C:3]([C:9]1[CH:10]=[CH:11][C:12]([CH2:13][N:14]2[CH2:15][CH2:16][CH:17]([C:20]([C:22]3[CH:23]=[CH:24][C:25]([NH:28][C:29](=[O:31])[CH3:30])=[CH:26][CH:27]=3)([OH:21])[CH3:36])[CH2:18][CH2:19]2)=[CH:32][CH:33]=1)([OH:8])[C:4]([F:7])([F:6])[F:5]

Participants

5

Reactant 3

HCID 3283Diethyl Ether2×HCID 86670972HCID 86670972, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 86670973HCID 86670973, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

N-(4-(1-(4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)benzyl)piperidine-4-carbonyl)phenyl)acetamide (1.702 mmol, 855 mg) was dissolved in anhydrous tetrahydrofuran (20 mL) under nitrogen and cooled to −78° C. 3M methylmagnesium bromide in diethyl ether (3.40 mmol, 1.134 mL) was added and the mixture stirred at −78° C. for 30 minutes before allowing to warm to room temperature and stirring for a further 4 hours. After this time, further 3M methylmagnesium bromide in diethyl ether (3.40 mmol, 1.134 mL) was added and the mixture stirred for 2 hours. The mixture was cooled to 0° C. and quenched with a saturated solution of ammonium chloride (30 mL). The mixture was extracted with ethyl acetate (100 mL) and washed with water (30 mL) then brine (30 mL). The organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting with dichloromethane to 15% methanol/dichloromethane) to afford the title compound (300 mg). MS (ESI) m/z 519.2 [M+H]+

Workup

  1. temperatureto warm to room temperature
  2. stirringstirring for a further 4 hours
  3. stirringthe mixture stirred for 2 hours
  4. temperatureThe mixture was cooled to 0° C.
  5. customquenched with a saturated solution of ammonium chloride (30 mL)
  6. extractionThe mixture was extracted with ethyl acetate (100 mL)
  7. washwashed with water (30 mL)
  8. dry with materialThe organics were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified by silica gel column chromatography (eluting with dichloromethane to 15% methanol/dichloromethane)

Sources & evidence

ORD record
ord-8431e6e12b564808ba0469b89883a337
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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