Cesium carbonate → 6-bromo-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528600Notes

Reaction equation

HRID 528600 reaction equation
[Br:1][C:2]1[C:11]([S:12]([N:15]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:16]2[S:17][CH:18]=[CH:19][N:20]=2)(=[O:14])=[O:13])=[CH:10][C:5]2[O:6][CH2:7][CH2:8][NH:9][C:4]=2[CH:3]=1.Br[C:31]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:32]=1[O:41][CH3:42].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:1][C:2]1[C:11]([S:12]([N:15]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:16]2[S:17][CH:18]=[CH:19][N:20]=2)(=[O:14])=[O:13])=[CH:10][C:5]2[O:6][CH2:7][CH2:8][N:9]([C:31]3[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:32]=3[O:41][CH3:42])[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 49911451-Bromo-2-methoxy-4-(trifluoromethyl)benzeneHCID 897618236-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 897619566-bromo-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 46.3%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A vial was charged with 6-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (107.43 mg, 0.216 mmol), 1-bromo-2-methoxy-4-(trifluoromethyl)benzene (Sigma-Aldrich, St. Louis, Mo., 193 mg, 0.757 mmol), Xantphos (25.04 mg, 0.043 mmol), Pd2(dba)3 (19.82 mg, 0.022 mmol), and cesium carbonate (212 mg, 0.649 mmol). The vessel was flushed with Ar (g), then 1,4-dioxane (2164 μl) was added. The vessel was sealed and placed in a 100° C. heating bath for 20 h. The mixture was cooled to room temperature, diluted with EtOAc, and filtered through celite. The filtrate was concentrated, and the residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-50% EtOAc/Heptane) to give 6-bromo-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (67 mg, 0.100 mmol, 46.2% yield) as a yellow foam: m/z (ESI) 670.2 (M+H)+.

Workup

  1. customThe vessel was flushed with Ar (g)
  2. addition1,4-dioxane (2164 μl) was added
  3. customThe vessel was sealed
  4. customplaced in a 100° C.
  5. temperatureheating bath for 20 h
  6. additiondiluted with EtOAc
  7. filtrationfiltered through celite
  8. concentrationThe filtrate was concentrated
  9. customthe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-e322cdd175624bd7bb1d25a443e0f02f
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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