Sodium Hydroxide → {4-[1-(4-Fluoro-phenyl)-1H-indol-5-yloxy]-butyl}-methyl-pyridin-4-yl-amine

HRID 1633713Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][NH:22][CH3:23])=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2C2C=CC=CC=2)C2CCCCC2)CCCCC1.CC(C)([O-])C.[Na+].Cl.Br[C:57]1[CH:62]=[CH:61][N:60]=[CH:59][CH:58]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]([CH3:23])[C:57]4[CH:62]=[CH:61][N:60]=[CH:59][CH:58]=4)=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 30 mg (0.091 mmol) {4-[1-(4-Fluoro-phenyl)-1H-indol-5-yloxy]-butyl}-methylamine, 2 mg (0.009 mmol) Pd(OAc)2, 7 mg (0.02 mmol) (dicyclohexylphosphino)-biphenyl, 44 mg (0.46 mmol) sodium tert-butoxide, and 20 mg (0.1 mmol) 4-bromopyridine hydrochloride in 1 ml of degassed toluene was stirred in a pressure tube at 120° C. during 16 hours. After cooling to room temperature the mixture was treated with 0.5M aqueous NaOH and extracted three times with Et2O. Drying of the combined organic layers with Na2SO4, evaporation of the solvent, and column chromatography on silica gel with EtOAc/NEt3 100:3 gave 30 mg (81%) of {4-[1-(4-Fluoro-phenyl)-1H-indol-5-yloxy]-butyl}-methyl-pyridin-4-yl-amine as a light yellow oil, MS: 390 (MH+). (In analogy to L. Buchwald et al. J. Org. Chem. 2000, 65, 1158-1174).

Workup

temperatureAfter cooling to room temperature the mixture
extractionextracted three times with Et2O
dry with materialDrying of the combined organic layers with Na2SO4, evaporation of the solvent, and column chromatography on silica gel with EtOAc/NEt3 100:3

Sources & evidence

ORD record: ord-18f069a3044a4cc688b73f7a52cbab99
Source dataset: uspto-grants-2003_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06503907B2

Reaction notes

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