Ammonium Chloride → 2-(6-Amino-7-fluoro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

HRID 518975Notes

Reaction equation

HRID 518975 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH:5]([N:7]1[C:12]2[CH:13]=[C:14]([N+:18]([O-])=O)[C:15]([F:17])=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[S:21])[CH3:6])[CH3:2].[Cl-].[NH4+]>CO.C1COCC1.[Zn]>[CH2:1]([O:3][C:4](=[O:22])[CH:5]([N:7]1[C:12]2[CH:13]=[C:14]([NH2:18])[C:15]([F:17])=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[S:21])[CH3:6])[CH3:2]

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 867273242-(7-Fluoro-6-nitro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Product 1

HCID 867273252-(6-Amino-7-fluoro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl esterYield 16.5%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(7-fluoro-6-nitro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (3.05 g, 9.29 mmol) in MeOH (45 ml) and THF (45 mL) was added zinc powder (6.07 g, 92.9 mmol) and ammonium chloride (4.97 g, 92.9 mmol). The reaction mixture was heated to reflux for 3 h then cooled to ambient temperature. The reaction mixture was filtered through a pad of Celite® and the filtrate was concentrated in vacuo. The residue was purified by column on silica gel (eluting with 0-30% EtOAc in petroleum ether to give 2-(6-amino-7-fluoro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (0.458 g, 16%). 1H NMR (DMSO-d6, 400 MHz): δ 6.89 (d, J=11.2 Hz, 1H), 6.61 (d, J=8.4 Hz, 1H), 6.21 (brs, 1H), 5.04 (brs, 2H), 4.78 (s, 2H), 3.99-4.03 (m, 2H), 1.62 (d, J=7.2 Hz, 3H), 1.07 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 3 h
  3. filtrationThe reaction mixture was filtered through a pad of Celite®
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by column on silica gel (
  6. washeluting with 0-30% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-5f321b4ed4ab476cab98623481a38623
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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