Hydrochloric Acid → 3-Hydroxy-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic Acid Methyl Ester

To a solution of 3.17 ml methoxyacetic acid methyl ester (31.4 mmol) in 30 ml of THF, 17 ml of LDA (2M in THF/heptane/ethylbenzene, 34.2 mmol) were added dropwise within 15 min at −78° C. After stirring for additional 15 min, a solution of 5.00 g of 4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-carbaldehyde (13.7 mmol) in 70 ml of dichloromethane was added dropwise within 20 min. The dark brown reaction solution was stirred for additional 60 min, then warm up to room temperature within 150 min, cooled to 0° C. again and treated with 50 ml of ice water and 6 ml of conc. hydrochloric acid (pH 3). The organic layer was separated, washed with 25 ml water, dried over sodium sulfate and evaporated to dryness to yield 8.81 g of crude product as a brown oil. Flash chromatography (SiO2, dichloromethane/AcOEt=9/1) yielded 5.89 g (91%) of the title compound as a syn/anti mixture of 1:4 with a purity of 98.3% (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); samples silylated with BSTFA/pyridine. Retention times: starting material (aldehyde 1), 23.8 min; syn-alcohol 6, 28.1 min; anti-alcohol 6, 28.5 min) as a yellowish crystalline solid.

1. stirringThe dark brown reaction solution was stirred for additional 60 min
2. temperaturecooled to 0° C. again
3. customThe organic layer was separated
4. washwashed with 25 ml water
5. dry with materialdried over sodium sulfate
6. customevaporated to dryness
7. customto yield 8.81 g of crude product as a brown oil

ORD record

ord-42c3604f57b9474d8ee8ae12fff77b87

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07365207B2