Réaction #2254225

Équation de réaction

NaBH4

2-[(9R)-9-(Pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethan-1-amine

sodium sulfate

HCl

3-methoxythiophene-2-carboxaldehyde

→

[(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine monohydrochloride

Rendement 41.0%

Solvants

CH2Cl2

MeOH

Et2O

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGstirred for 10 minutes
2. 2
   workup.STIRRINGstirred 1 h
3. 3
   Autrefinally quenched with water
4. 4
   AutreThe organics were separated off
5. 5
   Autreevaporated
6. 6
   AutreThe crude residue was purified by a Gilson prep HPLC
7. 7
   AutreThe desired fractions collected
8. 8
   Concentrationconcentrated
9. 9
   AutreAfter lyophilization, residue was partitioned between CH2Cl2 and 2N NaOH
10. 10
    Autrethe organic layers were collected
11. 11
    workup.ADDITIONwas added
12. 12
    Autremajority of solvent evaporated under reduced pressure
13. 13
    AutreThe solid obtained
14. 14
    Lavagewas washed several times with Et2O
15. 15
    Autredried

Mode opératoire

Into a vial were added 2-[(9R)-9-(Pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethan-1-amine (500 mg, 1.92 mmole), 18 mL CH2Cl2 and sodium sulfate (1.3 g, 9.6 mmole). The 3-methoxythiophene-2-carboxaldehyde (354 mg, 2.4 mmole) was then added, and the mixture was stirred overnight. NaBH4 (94 mg, 2.4 mmole) was added to the reaction mixture, stirred for 10 minutes, and then MeOH (6.0 mL) was added, stirred 1 h, and finally quenched with water. The organics were separated off and evaporated. The crude residue was purified by a Gilson prep HPLC. The desired fractions collected and concentrated and lyophilized. After lyophilization, residue was partitioned between CH2Cl2 and 2N NaOH, and the organic layers were collected. After solvent was concentrated to half of the volume, 1.0 eq of 1N HCl in Et2O was added, and majority of solvent evaporated under reduced pressure. The solid obtained was washed several times with Et2O and dried to provide [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine monohydrochloride (336 mg, 41% yield, m/z 387.0 [M+H]+ observed) as a white solid. The NMR for Compound 140 is described herein.

Source