Hydrochloric Acid → Tributylammonium hydroxy-(4-hydroxy-benzo[b]thiophen-7-yl)-acetate

Temperatur

2.5 °C

A 2 L reactor equipped with a mechanical stirrer, a thermometer, a dropping funnel, a sensor connected to a pH-meter and an argon inlet was charged under argon with 76.2 g (500 mmol) of 4-Hydroxybenzothiophene and 617.1 g (1100 mmol) of a 10% KOH aqueous solution. To the dark solution were added at 0-5° C. within 30 min ca. 85.91 g (580 mmol) of a 50% glyoxylic acid solution in water. If necessary, more glyoxylic acid is added such that the pH of the solution at the end of the addition was 11.5. After stirring for 3 h at 0-5° C., 200 ml of tert-butyl methyl ether were added to the reaction mixture followed by ca. 70 ml of 25% HCl solution in water such that the pH was ca. 7.0. The biphasic mixture was filtered through Speedex, then ca. 70 ml of 25% HCl solution in water were added to the aqueous phase such that the pH was ca. 2.0. After addition of 450 ml of tert-butyl methyl ether the organic phase was separated at room temperature and the aqueous phase washed with tert-butyl methyl ether. The combined organic phases were concentrated to a volume of ca. 300 ml and the residue was diluted with 50 ml of tert-butyl methyl ether and 100 ml of acetonitrile. To the resulting clear solution was added portionswise at 20-30° C. within 1 h a solution of 93.6 g (500 mmol) of tributylamine in 100 ml of tert-butyl methyl ether under seeding with crystals of the product. The resulting suspension was stirred over night at 20-30° C. and then filtered off. The filter cake was washed with 160 ml of tert-butyl methyl ether/acetonitrile 3:1 and the crystals dried over night at 60° C./10 mbar to afford 108.9 g (53.1%) of tributylammonium hydroxy-(4-hydroxy-benzo[b]thiophen-7-yl)-acetate as white crystals with a m.p. of ca. 200° C. (dec.).

1. customA 2 L reactor equipped with a mechanical stirrer
2. filtrationThe biphasic mixture was filtered through Speedex
3. additionca. 70 ml of 25% HCl solution in water were added to the aqueous phase such that the pH was ca. 2.0
4. additionAfter addition of 450 ml of tert-butyl methyl ether the organic phase
5. customwas separated at room temperature
6. washthe aqueous phase washed with tert-butyl methyl ether
7. concentrationThe combined organic phases were concentrated to a volume of ca. 300 ml
8. additionthe residue was diluted with 50 ml of tert-butyl methyl ether and 100 ml of acetonitrile
9. stirringThe resulting suspension was stirred over night at 20-30° C.
10. filtrationfiltered off
11. washThe filter cake was washed with 160 ml of tert-butyl methyl ether/acetonitrile 3:1
12. customthe crystals dried over night at 60° C./10 mbar

ORD-Eintrag

ord-8b7b224f1d6e4ddd90cc9e36be16ec5d

Quelldatensatz

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07259176B2