Triacetoxyperiodinane → 1-(5-Fluoro-3-pyridyl)-4-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butane-1,3-dione

HRID 1478447Notes

Reaction equation

HRID 1478447 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:32])[CH2:9][C:10](=[O:31])[CH:11]=[C:12]2[CH2:17][CH2:16][N:15]([C:18](=[O:30])[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH3:29])[CH:20]=3)[CH2:14][CH2:13]2)[CH:5]=[N:6][CH:7]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:8](=[O:32])[CH2:9][C:10](=[O:31])[CH:11]=[C:12]2[CH2:13][CH2:14][N:15]([C:18](=[O:30])[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH3:29])[CH:20]=3)[CH2:16][CH2:17]2)[CH:5]=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 159087Triacetoxyperiodinane2×HCID 897046124-(5-Fluoro-3-pyridyl)-4-hydroxy-1-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butan-2-one

Product 1

HCID 897053021-(5-Fluoro-3-pyridyl)-4-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butane-1,3-dioneYield 66.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(5-fluoro-3-pyridyl)-4-hydroxy-1-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butan-2-one (475 mg, 1.08 mmol) in dichloromethane (15 mL) was cooled to 0° C. and treated with Dess-Martin periodinane (457 mg, 1.08 mmol). The reaction mixture was stirred for 30 min and was treated with additional Dess-Martin periodinane (150 mg, 0.35 mmol). The reaction mixture was stirred for 30 min and was quenched by the addition of saturated aqueous sodium sulfite. The mixture was extracted with dichloromethane (3×50 mL) and the combined organics were washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified on silica gel utilizing a gradient of 60-100% ethyl acetate in hexanes to yield 1-(5-fluoro-3-pyridyl)-4-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butane-1,3-dione (317 mg). 1H NMR (400 MHz, CDCl3) δ 16.25 (br s, OH), 8.81 (t, J=1.5 Hz, 1H), 8.52 (d, J=2.8 Hz, 1H), 7.82 (ddd, J=9.0, 2.7, 1.8 Hz, 1H), 7.18 (dd, J=11.4, 3.0 Hz, 2H), 6.76 (d, J=8.1 Hz, 1H), 6.08 (s, 1H), 5.86 (s, 1H), 4.50 (m, 1H), 3.65 (br s, 4H), 3.02 (br s, 2H), 2.36 (br s, 2H), 2.14 (s, 3H), 1.28 (d, J=6.0 Hz, 6H). ESI-MS m/z calc. 438.20, found 439.5 (M+1)+; Retention time: 2.15 minutes as a colorless oil (3 min run).

Workup

  1. stirringThe reaction mixture was stirred for 30 min
  2. customwas quenched by the addition of saturated aqueous sodium sulfite
  3. extractionThe mixture was extracted with dichloromethane (3×50 mL)
  4. washthe combined organics were washed with saturated aqueous sodium bicarbonate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified on silica gel utilizing a gradient of 60-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b68eca4aeefd42868a74e66acb11858a
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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