1-Bromo-4-fluorobenzene → HCID 58975036, compound

HRID 737038Notes

Reaction equation

HRID 737038 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[NH2:9][CH2:10][CH:11]1[CH2:14][N:13]([C:15]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([N:26]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:28]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:27]3)(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[O:16])[CH2:12]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.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]>[F:8][C:5]1[CH:6]=[CH:7][C:2]([NH:9][CH2:10][CH:11]2[CH2:12][N:13]([C:15]([C:17]3[CH:18]=[CH:19][C:20]([S:23]([N:26]4[C:34]5[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=5)[C:28]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)=[CH:27]4)(=[O:25])=[O:24])=[CH:21][CH:22]=3)=[O:16])[CH2:14]2)=[CH:3][CH:4]=1

Participants

7

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 58975139HCID 58975139, compound

Product 1

HCID 58975036HCID 58975036, compoundYield 18.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Add 1-bromo-4-fluorobenzene (220 μL, 350 mg, 2.0 mmol, 2.0 equiv) to a mixture of (3-aminomethyl-azetidin-1-yl)-[4-(3-phenyl-indole-1-sulfonyl)-phenyl]-methanone (446 mg, 1.00 mmol, 1 equiv), tris(dibenzylideneacetone)dipalladium(0) (23 mg, 0.025 mmol, 0.025 equiv), 2-(di-tert-butylphosphino)biphenyl (15 mg, 0.057 mmol, 0.050 equiv), and sodium tert-butoxide (120 mg, 1.2 mmol, 1.2 equiv) in anhydr toluene (4 mL) and heat at 100° C. for 19 h. After cooling, transfer the reaction mixture through a 0.45-μm filter disc to a column of silica gel (125 mm×25 mm dia.) and elute (10-100% EtOAc/hex) to yield 98 mg (18%) of [3-[(4-fluoro-phenylamino)-methyl]-azetidin-1-yl]-[4-(3-phenyl-indole-1-sulfonyl)-phenyl]-methanone as a light-yellow foam. 1H NMR indicated pure desired product. MS (m/e): 540.07 (M+1); 538.19 (M−1).

Workup

  1. temperatureAfter cooling
  2. filtrationfilter disc to a column of silica gel (125 mm×25 mm dia.)
  3. washelute (10-100% EtOAc/hex)

Sources & evidence

ORD record
ord-c3781fab86bc4ae4884c040010336637
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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