Hexamethyldisilazane → 1-(3-Indanyloxy-4-methoxyphenyl)propylamine

To an ice bath cooled stirred solution of 1,1,1,3,3,3-hexamethyldisilazane (2.7 mL, 13 mmol) in tetrahydrofuran (5 mL) under nitrogen, was added a hexane solution of butyl lithium (2.5M, 4.8 mL, 12 mmol) via syringe. The ice bath was removed and the solution was stirred for 25 minutes at room temperature. This solution then was added dropwise to an ice bath cooled solution of 3-indanyloxy-4-methoxybenzaldehyde (2.68 g, 10.0 mmol) in tetrahydrofuran (4 mL) and the mixture was stirred for one hour. An ethereal solution of ethylmagnesium bromide (3M, 6.7 mL, 20 mmol) then was added dropwise via syringe. The reaction mixture was heated at reflux and was monitored by HPLC (Waters Nova-Pak/EC 18 column, 3.9×150 mm, 4 micron, 1 mL/min, 240 nm, 40/60, CH3CN/0.1% H3PO4 (aq)). After 48 hours the reaction had reached completion and was allowed to cool to room temperature. The reaction mixture then was slowly poured into a saturated solution of ammonium chloride (80 mL). The resulting mixture was extracted with methylene chloride (3×15 mL) and the combined extracts were dried over magnesium sulfate and concentrated to afford the product which was further purified by flash column chromatography (silica gel, 250/10/1, methylene chloride/methanol/ammonium hydroxide) to afford 0.27 g (9%) of product as an orange solid.

1. temperatureTo an ice bath cooled
2. customThe ice bath was removed
3. additionThis solution then was added dropwise to an ice bath
4. stirringthe mixture was stirred for one hour
5. temperatureThe reaction mixture was heated
6. temperatureat reflux
7. waitAfter 48 hours the reaction had reached
8. temperatureto cool to room temperature
9. extractionThe resulting mixture was extracted with methylene chloride (3×15 mL)
10. dry with materialthe combined extracts were dried over magnesium sulfate
11. concentrationconcentrated
12. customto afford the product which
13. customwas further purified by flash column chromatography (silica gel, 250/10/1, methylene chloride/methanol/ammonium hydroxide)

ORD record

ord-a172f4e4b1614e5bac954c6d01d97ff6

Source dataset

uspto-grants-1998_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05728844