반응 #472870

ord-868d6e195fae4926be41ac6822cc3341

반응 방정식

O=C([O-])O.[Na+]
sodium hydrogen carbonate
O=CCn1c(=O)ccc2ncc(Br)cc21
(7-bromo-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde
CC(C)(C)OC(=O)N(Cc1cc2c(cn1)OCCO2)C1CCNCC1
tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate
CC(=O)O[BH-](OC(C)=O)OC(C)=O.[Na+]
sodium triacetoxyborohydride
CC(C)(C)OC(=O)N(Cc1cc2c(cn1)OCCO2)C1CCN(CCn2c(=O)ccc3ncc(Br)cc32)CC1
tert-butyl (1-(2-(7-bromo-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)carbamate
수율 71.5%

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    workup.STIRRINGthe mixture was stirred for 2 hours
  2. 2
    기타the organic layer was separated
  3. 3
    세척washed with a saturated aqueous sodium chloride solution
  4. 4
    건조dried over anhydrous magnesium sulfate
  5. 5
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure
  6. 6
    기타The resultant residue was purified by silica gel column chromatography
  7. 7
    세척, and gradient elution with hexane
  8. 8
    기타ethyl acetate=50:50 to 5:95, and then recrystallized in 24 mL of ethanol

실험 절차

To 7.00 g of (7-bromo-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde, a solution of 10.07 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate in 140 mL of chloroform and 1.57 g of acetic acid were added, and the mixture was stirred at room temperature for 19 hours, then, 8.77 g of sodium triacetoxyborohydride was added thereto and the mixture was stirred for 2 hours. To the reaction mixture, 140 mL of a saturated aqueous sodium hydrogen carbonate solution was added, the organic layer was separated, then washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using silica gel; Chromatorex-NH made by Fuji Silysia Chemical Ltd., and gradient elution with hexane:ethyl acetate=50:50 to 5:95, and then recrystallized in 24 mL of ethanol to obtain 11.26 g of tert-butyl (1-(2-(7-bromo-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)carbamate as a white solid.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08367831B2uspto-grants-2013_02