반응 #163417

반응 방정식

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

수율 41.0%

용매

CH2Cl2

MeOH

Et2O

반응 조건

후처리

1. 1
   workup.STIRRINGstirred for 10 minutes
2. 2
   workup.STIRRINGstirred 1 h
3. 3
   기타finally quenched with water
4. 4
   기타The organics were separated off
5. 5
   기타evaporated
6. 6
   기타The crude residue was purified by a Gilson prep HPLC
7. 7
   기타The desired fractions collected
8. 8
   농축concentrated
9. 9
   기타After lyophilization, residue was partitioned between CH2Cl2 and 2N NaOH
10. 10
    기타the organic layers were collected
11. 11
    workup.ADDITIONwas added
12. 12
    기타majority of solvent evaporated under reduced pressure
13. 13
    기타The solid obtained
14. 14
    세척was washed several times with Et2O
15. 15
    기타dried

실험 절차

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.

출처