反応 #2254225

反応方程式

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

収率 41.0%

溶媒

CH2Cl2

MeOH

Et2O

反応条件

後処理

1. 1
   workup.STIRRINGstirred for 10 minutes
2. 2
   workup.STIRRINGstirred 1 h
3. 3
   その他finally quenched with water
4. 4
   その他The organics were separated off
5. 5
   その他evaporated
6. 6
   その他The crude residue was purified by a Gilson prep HPLC
7. 7
   その他The desired fractions collected
8. 8
   濃縮concentrated
9. 9
   その他After lyophilization, residue was partitioned between CH2Cl2 and 2N NaOH
10. 10
    その他the organic layers were collected
11. 11
    workup.ADDITIONwas added
12. 12
    その他majority of solvent evaporated under reduced pressure
13. 13
    その他The solid obtained
14. 14
    洗浄was washed several times with Et2O
15. 15
    その他dried

実験手順

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.

出典