Lawesson's reagent → (R)-2-(6-nitro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

HRID 519130Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:21])[C@H:5]([N:7]1[C:12]2[CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[CH:15]=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=O)[CH3:6])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:31])=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:21])[C@H:5]([N:7]1[C:12]2[CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[CH:15]=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[S:31])[CH3:6])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of (R)-2-(6-nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (80.0 g, 272.0 mmol) and Lawesson's Reagent (66 g, 163.0 mmol) in toluene (1 L) was heated at 120° C. for 3 h. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluting with 3% EtOAc in petroleum ether) to give (R)-2-(6-nitro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (75.0 g, 89%) as a yellow solid. 1H NMR (CDCl3, 400 MHz): δ 8.06 (dd, J=2.4, 8.8 Hz, 1H), 7.87 (d, J=2.4 Hz, 1H), 7.21 (d, J=8.8 Hz, 1H), 6.71 (m, 1H), 5.06 (d, J=15.6 Hz, 2H), 4.32 (q, J=7.2 Hz, 2H), 1.76 (d, J=7.6 Hz, 3H), 1.28-1.21 (t, J=7.2 Hz, 3H). SFC (Table 2, Method 3) Rt=4.04 min.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
customthe solvent was removed in vacuo
customThe residue was purified by column chromatography on silica gel (eluting with 3% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-6ee8bda6a25c42988825807f41aa1084
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115151B2

Reaction notes

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