Methoxymethyl-triphenylphosphonium chloride → 8-Bromo-5-methoxymethylene-2,3,4,5-tetrahydrobenzo[b]thiepine

Temperature

-75 °C

16.68 g (1.6 eq.) of (methoxymethyl)triphenylphosphonium chloride was suspended in 75 ml of abs. THF and deprotonated between −15° C. and −5° C. by adding via syringe 29.5 ml of 1.6 M n-butyllithium (hexane, 1.55 eq.). The resultant red ylide solution was cooled to −75° C. and treated with 7.82 g (30.4 mmol) of 8-bromo-3,4-dihydro-2H-benzo[b]thiepin-5-one, dissolved in 15 ml of abs. THF. The mixture was then kept for 0.3 h at −78° C. and for 1.25 h at room temperature. Pouring onto crushed ice, twofold extraction with diethylether, washing the organic phase with water, drying over magnesium sulfate, filtration and evaporation of the solvents yielded a crude product which was purified by flash chromatography (SiO2, hexane/ethylacetate 95/5); thereby, 7.39 g of 8-bromo-5-methoxymethylene-2,3,4,5-tetrahydrobenzo[b]thiepine was obtained as E/Z-mixture which was hydrolyzed as follows:

1. dissolutiondissolved in 15 ml of abs
2. additionPouring
3. customonto crushed
4. extractionice, twofold extraction with diethylether
5. washwashing the organic phase with water
6. dry with materialdrying over magnesium sulfate, filtration and evaporation of the solvents
7. customyielded a crude product which
8. customwas purified by flash chromatography (SiO2, hexane/ethylacetate 95/5)

ORD record

ord-629b67e2130041bfb0baded40ad4ee4d

Source dataset

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06479670B1