Diphenyl carbonate → phenyl 7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

HRID 1777850Notes

Reaction equation

HRID 1777850 reaction equation
[CH3:1][O:2][CH:3]([O:14][CH3:15])[C:4]1[N:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][NH:11]2)=[CH:6][CH:5]=1.[C:16]1([O:22][C:23](=O)[O:24]C2C=CC=CC=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH3:15][O:14][CH:3]([O:2][CH3:1])[C:4]1[N:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][N:11]2[C:23]([O:22][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:24])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 7597Diphenyl carbonateHCID 2733832Lithium HexamethyldisilazideHCID 177501767-(Dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine2×

Product 1

HCID 118037161phenyl 7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 4, 2 g, 9.60 mmol) and diphenylcarbonate (4.11 g, 19.21 mmol) in THF (40 ml) at −15° C. was treated with LHMDS (1M in THF, 13.3 ml, 13.3 mmol) over 0.5 h. The reaction mixture was quenched with sat. aq. NH4Cl, extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by normal phase chromatography (80 g silica gel cartridge, heptanes/EtOAc 100:0 to 25:75) to give the title compound as a pale yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ 7.65 (d, 1H), 7.46-7.38 (m, 2H), 7.27-7.18 (m, 4H), 5.17 (s, 1H), 3.87-3.80 (m, 2H), 3.26 (s, 6H), 2.83 (t, 2H), 2.00-1.92 (m, 2H).

Workup

  1. customThe reaction mixture was quenched with sat. aq. NH4Cl
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by normal phase chromatography (80 g silica gel cartridge, heptanes/EtOAc 100:0 to 25:75)

Sources & evidence

ORD record
ord-1915276893d34b67809ca0e30bf080e3
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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