Acetone, oxime → HCID 22493731, compound

HRID 1816402Notes

Reaction equation

HRID 1816402 reaction equation
CC(C)([O-])C.[K+].[CH3:7][C:8](=[N:10][OH:11])[CH3:9].F[C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=1[C:21]([C:23]1[CH:28]=[C:27]([CH2:29][CH2:30][CH3:31])[C:26]([O:32][CH3:33])=[CH:25][C:24]=1[CH2:34][CH2:35][CH3:36])=[O:22]>C1COCC1>[CH3:20][O:19][C:17]1[CH:18]=[CH:13][C:14]([C:21](=[O:22])[C:23]2[CH:28]=[C:27]([CH2:29][CH2:30][CH3:31])[C:26]([O:32][CH3:33])=[CH:25][C:24]=2[CH2:34][CH2:35][CH3:36])=[C:15]([O:11][N:10]=[C:8]([CH3:9])[CH3:7])[CH:16]=1

Participants

5

Reactant 3

HCID 67180Acetone, oximeHCID 11348500HCID 11348500, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 22493731HCID 22493731, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of potassium tert-butoxide (2.18 g, 19.4 mmol, heat-gunned under high vacuum) in THF (60 mL) was added acetone oxime (1.42 g, 19.4 mmol). The white slurry was stirred at room temperature for 1 h and then a solution of (2-fluoro-4-methoxyphenyl)(4-methoxy-2,5-dipropylphenyl)methanone (2.23 g, 6.47 mmol) in THF (10 mL ) was added. The mixture was stirred at 65° C. for 3 h and then quenched with a small amount of water. Most of the THF was removed in vacuo and extraction was performed in EtOAc (3×60 mL) with 50% saturated brine (50 mL). The crude product was employed in the ensuing cyclization. A portion of the crude product was subjected to preparative TLC (15% EtOAc/hexanes) to yield the title compound as a light green oil: 1H NMR (300 MHz, CDCl3) δ 0.87 (t, 3H, J=7.2 Hz), 0.92 (t, 3H, J=7.1 Hz), 1.42 (s, 3H), 1.48 (m, 2H), 1.60 (m, 2H), 1.89 (s, 3H), 2.46 (t, 2H, J=7.7 Hz), 2.77 (t, 2H, J=7.9 Hz), 3.85 (s, 3H), 3.87 (s, 3H), 6.59 (dd, 1H, J=8.6, 2.5 Hz), 6.68 (s, 1H), 7.08 (d, 1H, J=2.4 Hz), 7.13 (s, 1H), 7.55 (d, 1H, J=8.6 Hz); MS m/e 398 (M+H)+.

Workup

  1. stirringThe mixture was stirred at 65° C. for 3 h
  2. customquenched with a small amount of water
  3. customMost of the THF was removed in vacuo and extraction

Sources & evidence

ORD record
ord-e11557ab456f4aaf9c77926955897e7c
Source dataset
uspto-grants-2005_04
Patent number
US06884814B2

Reaction notes

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