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 855954Notes

Reaction equation

HRID 855954 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 76%

Conditions

Temperature
0 °C

Procedure

A suspension of 81.05 g of methyl 2-methoxy-2-(triphenylphosphonium)acetate chloride (202.2 mmol), 8.62 g of lithium methylat (215.7 mmol) and 50.00 g of 4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-carbaldehyde (134.8 mmol) in 500 ml of DMF was heated for 24 hours at 75°. The light brown reaction solution was cooled to 0° C., the formed crystals were filtered off and purified as described in Example 1 to yield 46.76 g (76%) of the titled compound with a purity of 97.7% (GC area). The mother liquor, which contained according to GC 5.6 area-% E-ester 5, 1.3 area-% Z-ester 5 and 87.5 area-% triphenylphosphine was treated with 3.04 g of 2-methyl-5-tert.-butylthiophenol (16.8 mmol) and 2.76 g of α,α′-azo-isobutyronitril (16.8 mmol). The resulting dark brown solution was stirred for 16 h at 90° C. Additional 6.08 g of 2-methyl-5-tert.-butylthiophenol (33.6 mmol) and 5.42 of α,α′-azo-isobutyronitril (33.6 mmol) were added, the reaction solution stirred for additional 6 h at 90° C. and then cooled to room temperature. Under stirring, 200 ml water were added and the formed suspension cooled to 0° C. The solid was filtered off, digested in 100 ml of methanol at r.t. for 15 min, filtered off and washed with 100 ml of methanol in two portions. The light brown filter cake was dried to a constant weight of 7.72 g. Crystallization from 30 ml of DMF, afforded 5.62 g (9.3%) of the title compound with a purity of 99% (GC area) as light brown crystals.

Workup

  1. temperaturewas heated for 24 hours at 75°
  2. filtrationthe formed crystals were filtered off
  3. custompurified

Sources & evidence

ORD record
ord-80c0aa29362a40a9b2fcede7d6f9123a
Source dataset
uspto-grants-2007_08
Patent number
US07262303B2

Reaction notes

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