Dimethyl Sulfoxide → HCID 19348475, compound

Temperature

-78 °C

A solution of 14.0 ml (0.20 mol) of dimethyl sulfoxide in 50 ml of methylene chloride was added dropwise over a period of 35 minutes to a solution of 9.0 ml (0.10 mol) of oxalyl chloride in 100 ml of methylene chloride cooled to -78° C., whilst the internal temperature of the mixture was kept below -60° C. The resulting mixture was then stirred at -78° C. for 30 minutes, after which a solution of 30.65 g (86.9 mmol) of 1-(4-t-butyldimethylsilyloxymethyl-2-methoxyphenyl)hexyl alcohol [prepared as described in step (i) above] in 60 ml of methylene chloride was added dropwise at the same temperature over a period of 35 minutes. The mixture was then stirred for 30 minutes. 60 ml (0.43 mol) of triethylamine were added dropwise to the mixture at the same temperature over a period of 17 minutes, and then the reaction mixture was stirred for 10 minutes, after which the dry ice-acetone bath was removed and the mixture was stirred for a further 50 minutes. At the end of this time, the reaction was terminated by adding water. The reaction mixture was then diluted with methylene chloride, and the organic phase was separated and then washed with 2 N aqueous hydrochloric acid, with water and with a saturated aqueous solution of sodium hydrogencarbonate, in that order, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 250 g of silica gel, using a 1:9 by volume mixture of ethyl acetate and hexane as the eluent, to give 27.84 g (yield 91%) of the title compound as an oily substance.

1. customwas kept below -60° C
2. stirringThe mixture was then stirred for 30 minutes
3. stirringthe reaction mixture was stirred for 10 minutes
4. customafter which the dry ice-acetone bath was removed
5. stirringthe mixture was stirred for a further 50 minutes
6. customAt the end of this time, the reaction was terminated
7. additionby adding water
8. additionThe reaction mixture was then diluted with methylene chloride
9. customthe organic phase was separated
10. washwashed with 2 N aqueous hydrochloric acid, with water and with a saturated aqueous solution of sodium hydrogencarbonate, in that order
11. dry with materialafter which it was dried over anhydrous magnesium sulfate
12. customThe solvent was then removed by distillation under reduced pressure
13. customthe resulting residue was purified by column chromatography through 250 g of silica gel
14. additionby volume mixture of ethyl acetate and hexane as the eluent

ORD record

ord-0c798dc3b9b343a1be88f278df30c123

Source dataset

uspto-grants-2000_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06040339