Diethyl Carbonate → tert-butyl 7-(2-ethoxy-2-oxoethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

HRID 897135Notes

Reaction equation

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

Participants

Conditions

Temperature: -78 °C

Procedure

The compound was prepared according to the procedure as described in WO 0033838. To a solution of 2-methyl-8-(tert-butoxycarbonyl)-5,6,7,8-tetrahydro-1,8-naphthyridine (1.4 g, 5.6 mmol) and diethylcarbonate (2.5 g, 20 mmol) in THF (10 ml) was added LDA (8 ml of 2M solution in hexane) at −78° C. and stirred at −78° C. for 40 minutes. The reaction was quenched with saturated NH4Cl and extracted with ethylacetate (2×100 ml). Combined organic solution was concentrated and purified on silica gel column to give 1.5 g (83%) yellow oil. NMR (CD3OD) δ 1.25 (t, 3H, J=7.10 Hz), 1.51 (s, 9H), 1.88-1.97 (m, 2H), 2.75 (t, 2H, J=6.59 Hz), 3.74-3.80 (m, 4H), 4.10-4.20 (m, 2H), 7.0 (d, 1H, J=7.61Hz), 7.39 (d, 1H, J=7.47 Hz).

Workup

customThe compound was prepared
customThe reaction was quenched with saturated NH4Cl
extractionextracted with ethylacetate (2×100 ml)
concentrationCombined organic solution was concentrated
custompurified on silica gel column

Sources & evidence

ORD record: ord-4938029f7d45418aba0e3e6f3842e350
Source dataset: uspto-grants-2005_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06921767B2

Reaction notes

Loading…