1-Bromo-2-ethylbenzene → 4-(2-ethylphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528667Notes

Reaction equation

HRID 528667 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[CH2:36][CH3:37].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.O.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]>[CH2:36]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[N:20]1[CH2:19][CH2:18][O:17][C:16]2[CH:21]=[C:12]([S:9]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:28][CH:27]=3)[C:22]3[S:23][CH:24]=[CH:25][N:26]=3)(=[O:11])=[O:10])[CH:13]=[CH:14][C:15]1=2)[CH3:37]

Participants

8

Reactant 4

HCID 160891-Bromo-2-ethylbenzeneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 897613484-(2-ethylphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 33%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 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 (1.0 g, 2.39 mmol), 1-bromo-2-ethylbenzene (572.0 mg, 3.11 mmol, Aldrich), Pd2(dba)3 (218 mg, 0.23 mmol, GLR), Xantphos (276 mg, 0.46 mmol, GLR) and sodium-tert-butoxide (458 mg, 4.784 mmol) in toluene (20 mL) was degassed with nitrogen for 10 minutes. The reaction mixture was heated at 100° C. for 1 h under microwave irradiation. After completion, reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×50 mL). The combined 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 obtain 4-(2-ethylphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (400 mg, 33%) as a brown solid. MS (ESI, positive ion) m/z; 522.1 (M+1)

Workup

  1. customwas degassed with nitrogen for 10 minutes
  2. customAfter completion, reaction mixture
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. dry with materialThe combined 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-4b9fe35782b5410584ca0a485e1dc510
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

Loading…