Acetic Acid → 4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride

HRID 528640Notes

Reaction equation

HRID 528640 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]2[N:10]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=3[O:21][CH3:22])[C:9](=[O:23])[CH2:8][O:7][C:6]=2[CH:24]=1.[ClH:25].C(O)(=O)C.N([O-])=O.[Na+].O.[N-]=[N+]=[N-].[S:38](=[O:40])=[O:39]>[Cl-].[Na+].O.[Cu]Cl.CCOC(C)=O>[CH3:22][O:21][C:12]1[CH:13]=[C:14]([C:17]([F:20])([F:19])[F:18])[CH:15]=[CH:16][C:11]=1[N:10]1[C:9](=[O:23])[CH2:8][O:7][C:6]2[CH:24]=[C:2]([S:38]([Cl:25])(=[O:40])=[O:39])[CH:3]=[CH:4][C:5]1=2

Participants

11

Reactant 7

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 962WaterHCID 1119Sulfur DioxideHCID 33558AzideHCID 23668193Sodium NitriteHCID 897616957-amino-4-(2-methoxy-4-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazin-3(4H)-one

Product 1

HCID 897619204-(2-methoxy-4-(trifluoromethyl)phenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chlorideYield 59.6%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 7-amino-4-(2-methoxy-4-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (1.4 g, 4.14 mmol) in hydrogen chloride (2.096 ml, 24.83 mmol) and acetic acid (4.74 ml, 83 mmol) in a 250 mL rbf and cooled to 0° C. Added sodium nitrite (0.314 g, 4.55 mmol) dissolved in water (0.746 ml, 41.4 mmol) and let stir at 0° C. for 30 min until azide formation by LCMS. Then bubbled sulfur dioxide (0.265 g, 4.14 mmol) gas into solution for 5 minutes and added copper(I) chloride (0.205 g, 2.069 mmol), then bubbled more sulfur dioxide into the solution for 5 minutes. Let stir at rt for 3 hr until reaction was complete by LCMS. Quenched reaction over ice, added EtOAc (100 mL) and brine (100 mL) and extracted 3 times with EtOAc (3×100 mL). Dried organics over Na2SO4 and concentrated via rotary evaporation. Purified 4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (1.041 g, 2.468 mmol, 59.6% yield) via MPLC with a gradient Hex:EtOAc column (0-100%) which was isolated as an off-white solid.

Workup

  1. custombubbled more sulfur dioxide into the solution for 5 minutes
  2. customQuenched
  3. customreaction over ice
  4. extractionextracted 3 times with EtOAc (3×100 mL)
  5. concentrationDried organics over Na2SO4 and concentrated via rotary evaporation

Sources & evidence

ORD record
ord-9af80b207c624ba896b529d637e4d9ce
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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