Dimethylformamide → (Z)-2-Methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic Acid Methyl Ester

HRID 855953Notes

Reaction equation

HRID 855953 reaction equation
[Li+].[CH3:2][O-:3].[CH3:4][C:5]1[O:9][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:7][C:6]=1[CH2:16][CH2:17][O:18][C:19]1[C:27]2[CH:26]=[CH:25][S:24][C:23]=2[C:22](C=O)=[CH:21][CH:20]=1.CN([CH:33]=[O:34])C>>[CH3:2][O:3][C:33](=[O:34])/[C:8](/[O:9][CH3:5])=[CH:10]/[C:22]1[C:23]2[S:24][CH:25]=[CH:26][C:27]=2[C:19]([O:18][CH2:17][CH2:16][C:6]2[N:7]=[C:8]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[O:9][C:5]=2[CH3:4])=[CH:20][CH:21]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 4177230Lithium methanolateHCID 111759364-[2-(5-Methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophene-7-carbaldehyde

Product 1

HCID 11259455(Z)-2-Methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic Acid Methyl EsterYield 73%

Conditions

Temperature
75 °C

Procedure

A suspension of 6.39 g (15.9 mmol) of methyl 2-methoxy-2-(triphenylphosphonium)-acetate chloride (Prepared from methyl 2-chloro-2-methoxyacetate and triphenylphosphine, in analogy to: P. Seneci, I. Leger, M. Souchet, G. Nadler, Tetrahedron 1997, 53, 17097-17114), 0.68 g of lithium methylat (17.0 mmol) and 3.89 g of 4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-carbaldehyde (10.6 mmol) in 40 ml of DMF was heated for 23 h at 75° C. The light brown reaction solution was cooled to 0° C., the formed white crystals were filtered off, washed with 40 ml of methanol and dried to constant weight (20° C./1 mbar/16 h) to afford 3.54 g (73%) of the title compound with a purity of 97.5% (GC area; Method: column: DB-1 (15 m*0.32 mm); injector: 270° C.; detector: 320° C.; oven 150-310° C. (4° C./min); carrier gas: H2 (60 KPa). Retention times: starting material (aldehyde 1), 23.8 min; E-ester 5, 28.8 min; Z-ester 5, 30.8 min). m.p.: 165° C. MS: 450.3 (M+H)+. 1H-NMR (CDCl3): 2.40 (s, 3H); 3.08 (t, J=6.5, 2H); 3.78 (s, 3H); 3.88 (s, 3H); 4.45 (t, J=6.5, 2H); 6.86 (d, J=8.4, 1H); 7.21 (s, 1H); 7.34 (d, J=5.5, 1H); 7.38-7.45 (m, 3H); 7.49 (d, J=5.5, 1H); 7.95-8.00 (m, 2H); 8.10 (d, J=8.4, 1H).

Workup

  1. temperatureThe light brown reaction solution was cooled to 0° C.
  2. filtrationthe formed white crystals were filtered off
  3. washwashed with 40 ml of methanol
  4. customdried to constant weight (20° C./1 mbar/16 h)

Sources & evidence

ORD record
ord-f21f241a3d4f4a318a8feb1ef930fd8a
Source dataset
uspto-grants-2007_08
Patent number
US07262303B2

Reaction notes

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