Lawesson's reagent → HCID 86727390, compound

HRID 519028Notes

Reaction equation

HRID 519028 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([O:13][C:14]2[C:15]([F:32])=[CH:16][C:17]3[O:22][CH2:21][C:20](=O)[N:19]([CH:24]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH3:25])[C:18]=3[CH:31]=2)([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:42])=CC=1>C1(C)C=CC=CC=1.COCCOC>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([O:13][C:14]2[C:15]([F:32])=[CH:16][C:17]3[O:22][CH2:21][C:20](=[S:42])[N:19]([CH:24]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH3:25])[C:18]=3[CH:31]=2)([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 87949Lawesson's reagentHCID 86727389HCID 86727389, compound

Product 1

HCID 86727390HCID 86727390, compoundYield 58.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 3-[4-(1-ethoxycarbonyl-ethyl)-7-fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yloxy]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.164 g, 0.362 mmol) in toluene (3 mL) and DME (3 mL) was added Lawesson's reagent (0.117 g, 0.290 mmol) and the mixture was heated to reflux for 4 h. The mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 5% to 10% EtOAc in petroleum ether) to give 3-[4-(1-ethoxycarbonyl-ethyl)-7-fluoro-3-thioxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yloxy]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.080 g, 47%) as a pale yellow solid. 1H NMR (CDCl3, 400 MHz): δ 6.82 (d, J=10.0 Hz, 1H), 6.72 (brs, 1H), 6.47 (d, J=6.8 Hz, 1H), 4.89 (d, J=13.2 Hz, 2H), 4.16 (m, 4H), 3.85 (m, 2H), 1.64 (d, J=7.2 Hz, 3H), 1.56 (s, 3H), 1.43 (s, 9H), 1.16 (t, J=6.8 Hz, 3H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 4 h
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica gel (eluting with 5% to 10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-4e0a2f72c90f40bf88835d5735706ee6
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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