Tetrahydrofuran → (R)-2-[(4R,5S,6R)-6-((E)-3,3-dimethylbut-1-enyl)-5-hydroxy-2,2-dimethyl-1,3-dioxan-4-yl]-2-methoxy-N-(2-methyl-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepin-4-yl)acetamide

Participants

Reaction Steps

A mixture of 25 mg (0.13 mmol) of product 3, 22 mg (0.13 mmol) of sodium 2-ethylhexanoate and 25 mg (0.088 mmol) of lactone 4 (which may be prepared according to the procedures described in J. Med. Chem, 2001, 44, 3692-3699, starting with the γ-lactone of α-glucoheptonic acid, and the content of which is incorporated herein by reference) in 2 ml of THF are stirred at room temperature under nitrogen. The reaction is continued until the amine 3 has disappeared (about 92 hours), the presence of which is monitored by TLC (90/10 v/v dichloromethane/methanol). After addition of 20 ml of ethyl acetate, the organic phase is washed with 20 ml of saturated aqueous NaCl solution, dried over magnesium sulfate and filtered, and the solvents are then evaporated off under reduced pressure. The residue is purified by chromatography on silica gel, eluting with a 97.5/2.5 v/v dichloromethane/methanol mixture to give a resin. This resin is dissolved in 20 ml of CH2Cl2, washed with 15 ml of 1N NaOH, 15 ml of saturated NaCl solution, dried over MgSO4, filtered and evaporated under reduced pressure to give 24 mg (59%) of the expected product 5 in the form of a resin (2 diastereoisomers).

Provenance & Evidence