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

HRID 519235Notes

Reaction equation

HRID 519235 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[C@H:5]([N:7]1[C:12]2[CH:13]=[C:14]([Br:17])[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:29])=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:19])[C@H:5]([N:7]1[C:12]2[CH:13]=[C:14]([Br:17])[CH:15]=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[S:29])[CH3:6])[CH3:2]

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 86727635(R)-2-(6-bromo-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Product 1

HCID 86727636(R)-2-(6-bromo-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl esterYield 144.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of (R)-2-(6-bromo-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (82.4 g, 252 mmol) and Lawesson's reagent (61.1 g, 151 mmol) in toluene (900 mL) was heated at reflux for 3 h and then cooled to ambient temperature. The solvent was removed in vacuo and the residue was purified by chromatography on silica gel (eluting with 5-10% EtOAc in petroleum ether) to give (R)-2-(6-bromo-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (75.2 g, 87%) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 7.19 (d, J=8.8 Hz, 1H), 7.04 (s, 1H), 6.93 (d, J=8.8 Hz, 1H), 6.57 (m, 2H), 4.96-4.87 (m, 2H), 4.29-4.16 (m, 2H), 1.71 (d, J=6.8 Hz, 3H), 1.18 (t, J=6.8 Hz, 3H). SFC (Table 1, Method 29) Rt=3.529 min.; [α]D20=19.25 (C=0.002 g/mL in methanol).

Workup

  1. temperatureat reflux for 3 h
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by chromatography on silica gel (eluting with 5-10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-a36237c000b94dda978c995d3ddd045c
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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