Reaction #40396

Reaction equation

lithium borohydride

6-benzyloxy-8-(2-ethoxy-2-hydroxy-acetyl)-4H-benzo[1,4]oxazin-3-one

2-(3,4-difluorophenyl)-1,1-dimethylethylamine

dichloromethane

→

8-{2-[2-(3,4-difluorophenyl)-1,1-dimethylethylamino]-1-hydroxyethyl}-6-hydroxy-4H-benzo [1,4]oxazin-3-one

Solvents

tetrahydrofuran

tetrahydrofuran

water

Conditions

Workup

1. 1
   workup.STIRRINGstirred for a further hour
2. 2
   Filtrationfiltered through an EXTRELUT® column
3. 3
   workup.ADDITIONThe eluate containing the ethanol amine
4. 4
   workup.DISSOLUTIONThe residue is dissolved in methanol and hydrogenated with palladium on charcoal (10%) as catalyst at 2.5 bar and ambient temperature
5. 5
   OtherThen the catalyst is separated off
6. 6
   Otherthe crude product is purified by chromatography

Procedure

357 mg (1 mmol) of 6-benzyloxy-8-(2-ethoxy-2-hydroxy-acetyl)-4H-benzo[1,4]oxazin-3-one and 185 mg (1 mmol) of 2-(3,4-difluorophenyl)-1,1-dimethylethylamine are stirred for 30 minutes in 5 mL tetrahydrofuran at ambient temperature. It is cooled to 0° C. and, under an argon atmosphere, 1.5 mL of a 2 molar solution of lithium borohydride in tetrahydrofuran is added dropwise. The mixture is stirred for 30 minutes at ambient temperature, combined with 10 mL dichloromethane, and 3 mL water, stirred for a further hour and then filtered through an EXTRELUT® column. The eluate containing the ethanol amine is freed from solvent. The residue is dissolved in methanol and hydrogenated with palladium on charcoal (10%) as catalyst at 2.5 bar and ambient temperature. Then the catalyst is separated off and the crude product is purified by chromatography. White solid. Yield: 31 mg (6%, trifluoroethyl acetate); mass spectroscopy: [M+H]+=393.

Source