Acetic Anhydride → tert-butyl 8-acetoxy-2-chloro-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

HRID 467833Notes

Reaction equation

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

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 6-(tert-Butoxycarbonyl)-2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine 1-oxide (150 mg, 0.53 mmol) in acetic anhydride (2.5 mL, 26.3 mmol), was stirred and heated at 70° C. overnight under nitrogen atmosphere. DCM (20 mL) was added to the reaction mixture, and the resulting solution was washed sequentially with water, saturated aqueous NaHCO3 solution and brine, dried over anhydrous MgSO4, and concentrated under vacuum. The residue was purified by flash chromatography on silica gel eluting with 0% to 30% EtOAc in hexane to give the title compound (115 mg, 66.8% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.51 (9H, s), 2.13 (3H, s), 3.30-3.49 (1H, d, J=12.0 Hz), 4.25-4.40 (1H, m), 4.45-4.55 (1H, d, J=12.0 Hz), 5.20-5.00 (1H, m), 5.73 (1H, br. s), 7.34 (1H, d, J=8.22 Hz), 7.51 (1H, d, J=8.41 Hz) ppm; LC/MS m/z: 327 (M+1).

Workup

washthe resulting solution was washed sequentially with water, saturated aqueous NaHCO3 solution and brine
dry with materialdried over anhydrous MgSO4
concentrationconcentrated under vacuum
customThe residue was purified by flash chromatography on silica gel eluting with 0% to 30% EtOAc in hexane

Sources & evidence

ORD record: ord-880c90e9dadb4cc5ae3d4d71d46fa4f8
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623885B2

Reaction notes

Loading…