Reaktion #1900

Reaktionsgleichung

trans-7-chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid

N-methylmorpholine

sodium borohydride

ethyl chlorocarbonate

→

trans-7-chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-ethanol

Ausbeute 99.8%

Lösungsmittel

tetrahydrofuran

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise to the solution
2. 2
   workup.STIRRINGThe mixture was stirred for one hour at room temperature
3. 3
   Einengenconcentrated
4. 4
   workup.ADDITIONAfter the addition of 200 ml of 1N hydrochloric acid
5. 5
   Extraktionthe concentrate was extracted with 200 ml of ethyl acetate
6. 6
   WaschenThe organic layer was washed with a saturated sodium bicarbonate aqueous solution
7. 7
   Trocknendried over anhydrous magnesium sulfate
8. 8
   SonstigeThe solvent was evaporated off under reduced pressure
9. 9
   SonstigeThe residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=1:1)

Vorschrift

In 200 ml of tetrahydrofuran was dissolved 14.7 g of trans-7-chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid obtained in Example 2 and 4.51 ml of N-methylmorpholine. To the solution was added 3.92 ml of ethyl chlorocarbonate at -10° C.; the mixture was then stirred for 15 minutes. After the addition of 3.86 g of sodium borohydride, 200 ml of methanol was added dropwise to the solution. The mixture was stirred for one hour at room temperature and then concentrated. After the addition of 200 ml of 1N hydrochloric acid, the concentrate was extracted with 200 ml of ethyl acetate. The organic layer was washed with a saturated sodium bicarbonate aqueous solution and dried over anhydrous magnesium sulfate. The solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=1:1) to yield 14.2 g of trans-7-chloro-5-(2-chlorophenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-ethanol as colorless crystals, m.p. 157° to 159° C.

Quelle