Dimethylformamide dimethyl acetal → 2-(3-(3-Chlorophenyl)-1-(dimethylamino)-3-oxoprop-1-en-2-yl)isoindoline-1,3-dione

HRID 474337Notes

Reaction equation

HRID 474337 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:21])[CH2:9][N:10]2[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]2=[O:20])[CH:5]=[CH:6][CH:7]=1.CO[CH:24](OC)[N:25]([CH3:27])[CH3:26]>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:21])[C:9]([N:10]2[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]2=[O:20])=[CH:24][N:25]([CH3:27])[CH3:26])[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 580630902-(2-(3-Chlorophenyl)-2-oxoethyl)isoindoline-1,3-dione

Product 1

HCID 666775102-(3-(3-Chlorophenyl)-1-(dimethylamino)-3-oxoprop-1-en-2-yl)isoindoline-1,3-dioneYield 80%

Conditions

Temperature
100 °C

Procedure

A stirred mixture of 2-(2-(3-chlorophenyl)-2-oxoethyl)isoindoline-1,3-dione (782.2 mg, 2.610 mmol, 1 equiv) and 1,1-dimethoxy-N,N-dimethylmethanamine (1.5 mL, 11 mmol, 4.3 equiv) was heated at 100° C. for 18 hours. Excess 1,1-dimethoxy-N,N-dimethylmethanamine was removed by rotary evaporation. The crude product was purified by flash column chromatography on silica gel (50 to 100% ethyl acetate in heptane) to yield 740 mg (80%) of 2-(3-(3-chlorophenyl)-1-(dimethylamino)-3-oxoprop-1-en-2-yl)isoindoline-1,3-dione. LCMS (ESI) m+H=355.2; 1H NMR (400 MHz, CDCl3) δ: 7.90 (d of d, 2H), 7.77 (d of d, 2H), 7.57 (s, 1H), 7.44 (d, 1H), 7.37 (overlapping d and s, 2H), 7.31 (t, 1H), 3.00 (s, 6H).

Workup

  1. customExcess 1,1-dimethoxy-N,N-dimethylmethanamine was removed by rotary evaporation
  2. customThe crude product was purified by flash column chromatography on silica gel (50 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-79df89e5595d48b8885843a040457b26
Source dataset
uspto-grants-2014_01
Patent number
US08637526B2

Reaction notes

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