Boron trifluoride etherate → 4-(5-Fluoro-3-pyridyl)-4-hydroxy-1-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butan-2-one

HRID 1478446Notes

Reaction equation

HRID 1478446 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:9]=1)[CH:7]=[O:8].B(F)(F)F.CCOCC.[CH:19]([O:22][C:23]1[CH:40]=[CH:39][C:26]([C:27]([N:29]2[CH2:34][CH2:33][C:32](=[CH:35][C:36](=[O:38])[CH3:37])[CH2:31][CH2:30]2)=[O:28])=[CH:25][C:24]=1[CH3:41])([CH3:21])[CH3:20]>ClCCl>[F:1][C:2]1[CH:9]=[C:6]([CH:7]([OH:8])[CH2:37][C:36](=[O:38])[CH:35]=[C:32]2[CH2:33][CH2:34][N:29]([C:27](=[O:28])[C:26]3[CH:39]=[CH:40][C:23]([O:22][CH:19]([CH3:21])[CH3:20])=[C:24]([CH3:41])[CH:25]=3)[CH2:30][CH2:31]2)[CH:5]=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 141411595-Fluoropyridine-3-carbaldehydeHCID 897045461-[1-(4-Isopropoxy-3-methyl-benzoyl)-4-piperidylidene]propan-2-one

Product 1

HCID 897046124-(5-Fluoro-3-pyridyl)-4-hydroxy-1-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butan-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 5-fluoronicotinaldehyde (51 mg, 0.41 mmol) in dichloromethane (1.7 mL) was cooled to −78° C. and boron trifluoride diethyl etherate (164 μL, 0.82 mmol) was added. The mixture was stirred at −78° C. for 5 min. The solution from step 1 was added. The mixture was stirred at −78° C. for 5 min, quenched with a buffer solution of pH=7. The aqueous layer was extracted with dichloromethane (3×50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified on silica gel utilizing a gradient of 60-100% ethyl acetate in hexanes to afford 4-(5-fluoro-3-pyridyl)-4-hydroxy-1-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butan-2-one (105 mg). 1H NMR (400 MHz, CDCl3) δ 8.46-8.31 (m, 2H), 7.53-7.49 (m, 1H), 7.24-7.22 (m, 2H), 6.83 (d, J=8.1 Hz, 1H), 6.09 (s, 1H), 5.26 (dd, J=8.9, 5.9 Hz, 1H), 4.62-4.53 (m, 1H), 4.13-4.12 (m, 1H), 3.69 (br d, 4H), 3.00 (br s, 2H), 2.88 (d, J=6.2 Hz, 2H), 2.37 (br s, 2H), 2.21 (s, 3H), 1.36 (d, J=6.0 Hz, 6H). ESI-MS m/z calc. 440.21, found 441.4 (M+1)+; Retention time: 1.65 minutes (3 min run).

Workup

  1. stirringThe mixture was stirred at −78° C. for 5 min
  2. customquenched with a buffer solution of pH=7
  3. extractionThe aqueous layer was extracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified on silica gel utilizing a gradient of 60-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c05f07f209324b34ab7c3997643b0a1e
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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