Reaktion #2254225

Reaktionsgleichung

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

Ausbeute 41.0%

Lösungsmittel

CH2Cl2

MeOH

Et2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 10 minutes
2. 2
   workup.STIRRINGstirred 1 h
3. 3
   Sonstigefinally quenched with water
4. 4
   SonstigeThe organics were separated off
5. 5
   Sonstigeevaporated
6. 6
   SonstigeThe crude residue was purified by a Gilson prep HPLC
7. 7
   SonstigeThe desired fractions collected
8. 8
   Einengenconcentrated
9. 9
   SonstigeAfter lyophilization, residue was partitioned between CH2Cl2 and 2N NaOH
10. 10
    Sonstigethe organic layers were collected
11. 11
    workup.ADDITIONwas added
12. 12
    Sonstigemajority of solvent evaporated under reduced pressure
13. 13
    SonstigeThe solid obtained
14. 14
    Waschenwas washed several times with Et2O
15. 15
    Sonstigedried

Vorschrift

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.

Quelle