1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 89761916, compound

HRID 528660Notes

Reaction equation

HRID 528660 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.Br[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[O:36][CH2:37][O:38][CH3:39].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.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[N:20]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[O:36][CH2:37][O:38][CH3:39])[CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 113104791-Bromo-2-(methoxymethoxy)benzeneHCID 23676156Sodium t-butoxideHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2×

Product 1

HCID 89761916HCID 89761916, compoundYield 91.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (Intermediate M; 500 mg, 1.19 mmol), 1-bromo-2-(methoxymethoxy)benzene (1.2 g, 5.98 mmol), Pd2(dba)3 (109 mg, 0.119 mmol, GLR), Xantphos (138 mg, 0.23 mmol, GLR) and sodium-tert-butoxide (229 mg, 2.39 mmol) in toluene (15 mL) was degassed with nitrogen for 10 minutes. The reaction mixture was heated at 100° C. for 1 h under microwave. After completion, the reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (3×15 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the crude material which was purified by combiflash column chromatography (column size: 12 g; elution: 0-20% ethyl acetate in hexane) to yield N-(4-methoxybenzyl)-4-(2-(methoxymethoxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (600 mg, 90.7%). MS (ESI, positive ion) m/z; 554.1 (M+1).

Workup

  1. customwas degassed with nitrogen for 10 minutes
  2. additionAfter completion, the reaction mixture was diluted with water (15 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude material which
  7. customwas purified by combiflash column chromatography (column size: 12 g; elution: 0-20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-417da32ff6f84a93bcb40308123c0343
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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