反应详情

温度

120 °C

A solution of 16.50 g (56.24 mmol) of (3R,4R)-3-hydroxy-4-(4-hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butylester in 40 ml of dimethylformamide was treated in succession with 12.68 g (59.06 mmol) of 1-(3-chloro-propoxymethyl)-2-methoxy-benzene (WO 97/09311) and 12.44 g (89.99 mmol) of potassium carbonate. This mixture was stirred at 120° C. for 26 hours. Subsequently, it was filtered, concentrated to a few milliliters, poured into 300 ml of an ice/water mixture and extracted three times with 100 ml of methylene chloride each time. The combined organic phases were washed once with a small amount of water, dried over magnesium sulphate, evaporated under reduced pressure and dried in a high vacuum. The resulting crude product (31.64 g) was separated on silica gel using a 99:1 mixture of methylene chloride and methanol as the eluent and yielded 25.4 g (95.8% of theory) (3R,4R)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butylester as a slightly yellow oil; MS: 489 (M+NH4+).

1. filtrationSubsequently, it was filtered
2. concentrationconcentrated to a few milliliters
3. additionpoured into 300 ml of an ice/water mixture
4. extractionextracted three times with 100 ml of methylene chloride each time
5. washThe combined organic phases were washed once with a small amount of water
6. dry with materialdried over magnesium sulphate
7. customevaporated under reduced pressure
8. customdried in a high vacuum
9. customThe resulting crude product (31.64 g) was separated on silica gel using
10. additiona 99:1 mixture of methylene chloride and methanol as the eluent