Ethyl Acetate → 1-(1-Benzylpiperidin-4-yl)-4-(3,4-difluorophenyl)butane-1,3-dione

HRID 1068139Notes

Reaction equation

HRID 1068139 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:16])[CH3:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:17][C:18]1[CH:19]=[C:20]([CH2:25][C:26](OC)=[O:27])[CH:21]=[CH:22][C:23]=1[F:24].[H-].[Na+].CCOC(C)=O>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:16])[CH2:15][C:26](=[O:27])[CH2:25][C:20]2[CH:21]=[CH:22][C:23]([F:24])=[C:18]([F:17])[CH:19]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 9109231-(1-Benzylpiperidin-4-yl)ethanoneHCID 18187749Methyl 2-(3,4-difluorophenyl)acetate

Product 1

HCID 211929941-(1-Benzylpiperidin-4-yl)-4-(3,4-difluorophenyl)butane-1,3-dioneYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared in 67% yield from 2.18 g 1-benzyl-4-acetylpiperidine from the last step, 5.58 g methyl 3,4-difluorophenylacetate from Fisher esterification, and 0.8 g 60% NaH in 15 mL anhydrous THF using a procedure similar to that described in Example 1, Step A Method B. RF: 0.28 (15% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3): δ7.32˜7.35 (m, 4H), 7.26˜7.30 (m, 1H), 7.06˜7.15 (m, 3H), 6.95˜6.98 (m, 1H), 5.47 (s, 1H), 3.57 (s, 2H), 3.54 (br s, 2H), 2.96 (br d, 11.5 Hz, 2H), 2.17˜2.21 (m, 1H), 2.02˜2.10 (m, 2H), 1.70˜1.83 (m, 4H).

Sources & evidence

ORD record
ord-c713a29b211849caa1faa807f74a4353
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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