반응 #42907

반응 방정식

triethylamine

1-(tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinoline-4-carboxylic acid

1,2,3,4-tetrahydro-isoquinoline

Diethyl cyanophosphonate

→

desired product

수율 66.0%

[4-(3,4-Dihydro-1H-isoquinoline-2-carbonyl)-6,8-dimethoxy-isoquinolin-1-ylmethyl]-carbamic acid tert-butyl ester

수율 66.0%

용매

THF

EtOAc

THF

반응 조건

후처리

1. 1
   workup.WAITat room temperature for 15 h
2. 2
   세척washed with water
3. 3
   추출The aqueous layer was extracted with EtOAc
4. 4
   세척the combined organic layers were washed with NH4OH (10% solution in H2O)
5. 5
   건조The organic layer was then dried over magnesium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   기타The resulting residue was triturated with ether

실험 절차

According to the procedure of Yamada et al. (Note 2), a solution of 1-(tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinoline-4-carboxylic acid (100 mg, 0.3 mmol) and 1,2,3,4-tetrahydro-isoquinoline (44 mg, 0.33 mmol) in 5 mL of THF was stirred at 0° C. under a nitrogen atmosphere. Diethyl cyanophosphonate (54 mg, 0.33 mmol) in 2 mL of THF was added followed by triethylamine (77 μL, 0.55 mmol). The reaction was stirred at 0° C. for 30 minutes and then at room temperature for 15 h. The reaction was diluted with EtOAc and then washed with water. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with NH4OH (10% solution in H2O) and then with brine. The organic layer was then dried over magnesium sulfate, filtered and concentrated. The resulting residue was triturated with ether to give 87 mg (66%) of the desired product. H1-NMR (CDCl3): δ 8.30 (s, 1H), 7.27 (broad m, 4H), 6.75 (m, 1H), 6.58 (m, 2H), 5.09 (m, 2H), 4.41 (m, 2H), 3.98 (m, 2H), 3.83 (s, 2H), 3.50 (s, 3H), 3.09 and 2.77 (m, 1H each), 1.52 (s, 9H), [Note: broadening of peaks observed due to Boc group, rotamers also observed.] MS: APCI (M+H) calc'd for C27H31N3O5+H 478.6; found 478.0.

출처