Sodium Carbonate → 3,3-Dimethyl-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine-6-carbonitrile

HRID 1475390Notes

Reaction equation

C(OC([N:8]1[C:16]2[CH:15]=[C:14](Cl)[N:13]=[CH:12][C:11]=2[C:10]([CH3:19])([CH3:18])[CH2:9]1)=O)(C)(C)C.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.C(=O)([O-])[O-].[Na+].[Na+].[CH3:51][N:52]1C(=O)CCC1>[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[K+].[K+].[K+].[K+].[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:19][C:10]1([CH3:18])[C:11]2[CH:12]=[N:13][C:14]([C:51]#[N:52])=[CH:15][C:16]=2[NH:8][CH2:9]1

Participants

Conditions

Temperature: 185 °C

Procedure

A mixture of 6-chloro-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (0.405 g, 1.43 mmol), K4[Fe(CN)6](1.21 g, 2.86 mmol), Pd(OAc)2 (16 mg, 0.07 mmol), butyl di-1-adamantylphoshine (77 mg, 0.21 mmol) and sodium carbonate (0.304 g, 2.86 mmol) was slurried in NMP (14.3 mL) at ambient temperature. The reaction was heated under microwave irradiation at 185° C. for 2 h. The reaction was cooled to ambient temperature and filtered. The filtrate was dissolved in water and extracted with diethyl ether/petrol (1:1, 3×). The combined organic extracts were washed with brine (3×), dried over sodium sulfate, and solvent removed in vacuo. Chromatography (SiO2, gradient elution, 0-100%, EtOAc/petrol) gave the title compound (36 mg, 15%) as a colourless solid. MS: [M+H]+=174

Workup

temperatureThe reaction was cooled to ambient temperature
filtrationfiltered
dissolutionThe filtrate was dissolved in water
extractionextracted with diethyl ether/petrol (1:1, 3×)
washThe combined organic extracts were washed with brine (3×)
dry with materialdried over sodium sulfate, and solvent
customremoved in vacuo
washChromatography (SiO2, gradient elution, 0-100%, EtOAc/petrol)

Sources & evidence

ORD record: ord-e2e3c694db564c39a99cf518c727e0ad
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018214B2

Reaction notes

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