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

HRID 2200069Notes

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-0f2409f320394824877309627e7b8716
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359355B2

Reaction notes

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