Sodium Carbonate → benzyl 3-(1-hydroxy-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

HRID 470927

Reaktionsgleichung

Reaktionsgleichung von HRID 470927
[CH3:1][O:2][C:3](=[O:34])[C:4]([C:6]1[C:7]([CH3:33])=[N:8][C:9]2[CH2:10][CH2:11][N:12]([C:23]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:24])[CH2:13][C:14]=2[C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)=[O:5].[B]1OC2C(=CC=CC=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[OH:5][CH:4]([C:6]1[C:7]([CH3:33])=[N:8][C:9]2[CH2:10][CH2:11][N:12]([C:23]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[O:24])[CH2:13][C:14]=2[C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:3]([O:2][CH3:1])=[O:34]

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 6327445BenzcatechinboraneHCID 86692200benzyl 3-(2-methoxy-2-oxoacetyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate2×

Produkt 1

HCID 86692201benzyl 3-(1-hydroxy-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylateAusbeute 50,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-35 °C

Versuchsvorschrift

A solution of benzyl 3-(2-methoxy-2-oxoacetyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (2.53 g, 5.52 mmol) (intermediate 10) and 1M (toluene) R-5,5-diphenyl-2-methyl-3,4-propano-1,3,2-oxazaborlidine (2.21 ml, 2.21 mmol) in toluene (100 ml) was cooled to −35° C. Catecholborane (50 wt % in toluene) (1.65 ml, 7.73 mmol) was added dropwise and the solution stirred at −35° C. for 30 min then at −15° C. for 2 h. The reaction was diluted with EtOAc and stirred vigorously with sat'd Na2CO3 for 1 h. The organic phase was washed with twice with satd Na2CO3, dried (Na2SO4), filtered and concentrated. The resulting oil was purified by flash column chromatography (Biotage; 0%-100% EtOAc/hexane) to provide benzyl 3-(1-hydroxy-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (1.29 g, 50% yield) as a white foam. 1H NMR (400 MHz, CDCl3) δ ppm 7.20-7.49 (m, 7H), 7.08 (t, J=8.68 Hz, 2H), 5.11 (d, J=15.65 Hz, 3H), 4.22 (br. s., 2H), 3.67-3.89 (m, 5H), 3.14 (d, J=2.45 Hz, 1H), 2.99-3.11 (m, 2H), 2.55 (s, 3H), 2.43 (s, 3H). LCMS (M+H) calcd for C27H29N2O5: 461.20. found: 461.0.

Aufarbeitung

  1. waitat −15° C. for 2 h
  2. washThe organic phase was washed with twice with satd Na2CO3
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting oil was purified by flash column chromatography (Biotage; 0%-100% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-d9ca87fd5aa2490680c467ab3fd4208f
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629276B2

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