8-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester → 8-{5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carbonyl}-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester

HRID 419164Notes

Reaction equation

HRID 419164 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:13]2[CH:14]=[CH:15][CH:16]=[C:17]([CH:18]([C:20]3[C:25]([N:26]([S:30]([C:33]4[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([C:40]([F:43])([F:42])[F:41])[CH:34]=4)(=[O:32])=[O:31])[CH2:27][O:28][CH3:29])=[CH:24][C:23]([Cl:44])=[CH:22][N:21]=3)[OH:19])[C:12]=2[O:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>O1CCOCC1.O=[Mn]=O>[C:1]([O:5][C:6]([N:8]1[C:13]2[CH:14]=[CH:15][CH:16]=[C:17]([C:18]([C:20]3[C:25]([N:26]([S:30]([C:33]4[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([C:40]([F:43])([F:41])[F:42])[CH:34]=4)(=[O:32])=[O:31])[CH2:27][O:28][CH3:29])=[CH:24][C:23]([Cl:44])=[CH:22][N:21]=3)=[O:19])[C:12]=2[O:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 666489408-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester

Product 1

HCID 666490618-{5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carbonyl}-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl esterYield 82.9%

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 8-({5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester (562.7 mg, 0.91 mmol) in dioxane (4 mL) was added preactivated MnO2 (932.9 mg, 9.12 mmol), and the resulted mixture was heated at 80° C. for two hour. The resulted mixture was cooled to r.t., and filtered. The solid was washed with EtOAc (20 mL×3). EtOAc washing solution was combined with dioxane filtrate, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to provide 8-{5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carbonyl}-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester (510.2 mg) as yellow syrup. MS m/z: 676.0 (M+H)+.

Workup

  1. temperatureThe resulted mixture was cooled to r.t.
  2. filtrationfiltered
  3. washThe solid was washed with EtOAc (20 mL×3)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-2c443bbfe48649ecadec4dc25baebfb6
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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