4-Chlorophenol → HCID 131718786, compound

A mixture of (1R,2R,3S)-2-hydroxymethyl-3-(4-fluorophenyl)tropane (1.8 g, 7.2 mmol), p-toluen-sulphonylchloride (2 g, 10.5 mmol) and triethyl amine (1.6 ml, 12 mmol) in methylene chloride (50 ml) was stirred at room temperature for 20 hours and the reaction mixture was concentrated in vacuo. Water (50 ml) and diethyl ether (50 ml) was added and the mixture was stirred for 1/2 hour. The organic phase was washed once with sodium hydroxide (1M), twice with water, and was then dried and concentrated in vacuo. The remanescens was dissolved in a small amount of absolute ethanol and was, at room temperature, added to a solution of sodium 4-chloro-phenolate in absolute ethanol, made by addition of sodium (0.24 g, 10 mmol) to a solution of p-chlorophenol in absolute ethanol. The mixture was refluxed for three days and was concentrated in vacuo. The remanescens was stirred in a mixture of water and diethyl ether and the organic phase was washed with water. After drying and concentration in vacuo, the crude product was subjected to column chromatography first with ethyl acetate and later with ethyl acetate and methanol (10%) as eluent. An oil was isolated which was dissolved in a small amount of diethyl ether and the title compound was precipitated, by addition of hydrochloric acid in diethyl ether, as white crystals (hygroscopic), m.p. 70°-75° C.

1. concentrationthe reaction mixture was concentrated in vacuo
2. additionWater (50 ml) and diethyl ether (50 ml) was added
3. stirringthe mixture was stirred for 1/2 hour
4. washThe organic phase was washed once with sodium hydroxide (1M), twice with water
5. customwas then dried
6. concentrationconcentrated in vacuo
7. dissolutionThe remanescens was dissolved in a small amount of absolute ethanol
8. customwas, at room temperature
9. additionadded to a solution of sodium 4-chloro-phenolate in absolute ethanol
10. temperatureThe mixture was refluxed for three days
11. concentrationwas concentrated in vacuo
12. stirringThe remanescens was stirred in a mixture of water and diethyl ether
13. washthe organic phase was washed with water
14. customAfter drying
15. concentrationconcentration in vacuo
16. customAn oil was isolated which
17. customthe title compound was precipitated, by addition of hydrochloric acid in diethyl ether, as white crystals (hygroscopic), m.p. 70°-75° C.

ORD record

ord-9ac3f680b11445ae9a4132586831ecfc

Source dataset

uspto-grants-1995_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05444070