تفاعل #2254225

معادلة التفاعل

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

المردود 41.0%

المذيبات

CH2Cl2

MeOH

Et2O

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGstirred for 10 minutes
2. 2
   workup.STIRRINGstirred 1 h
3. 3
   أخرىfinally quenched with water
4. 4
   أخرىThe organics were separated off
5. 5
   أخرىevaporated
6. 6
   أخرىThe crude residue was purified by a Gilson prep HPLC
7. 7
   أخرىThe desired fractions collected
8. 8
   تركيزconcentrated
9. 9
   أخرىAfter lyophilization, residue was partitioned between CH2Cl2 and 2N NaOH
10. 10
    أخرىthe organic layers were collected
11. 11
    workup.ADDITIONwas added
12. 12
    أخرىmajority of solvent evaporated under reduced pressure
13. 13
    أخرىThe solid obtained
14. 14
    غسيلwas washed several times with Et2O
15. 15
    أخرىdried

الإجراء التجريبي

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.

المصدر