O-Cresol → 3,3-Dimethyl-6-o-tolyloxy-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

HRID 1475356Notes

Reaction equation

[C:1]([O:5][C:6]([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:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[OH:27].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14]([O:27][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[CH3:20])[N:13]=[CH:12][C:11]=2[C:10]([CH3:19])([CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

A vessel containing 6-chloro-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (100 mg, 0.35 mmol), 2-methyl-phenol (38 mg, 0.42 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (tBuXPhos) (5 mg, 0.01 mmol), Pd(OAc)2 (1.6 mg, 0.007 mmol) and potassium phosphate (150 mg, 0.70 mmol) in toluene (2 mL) was evacuated and flushed with nitrogen. The mixture was stirred at 110° C. overnight then were allowed to cool and then partitioned between EtOAc and water. The organic extract was washed with brine, dried (Na2SO4) and evaporated in vacuo. Chromatography (SiO2; gradient elution with 0-10% EtOAc in petrol) gave title compound (89 mg) {MS: [M+H]+=355} as an inseparable mixture with starting material.

Workup

customwas evacuated
customflushed with nitrogen
temperatureto cool
custompartitioned between EtOAc and water
extractionThe organic extract
washwas washed with brine
dry with materialdried (Na2SO4)
customevaporated in vacuo
washChromatography (SiO2; gradient elution with 0-10% EtOAc in petrol)

Sources & evidence

ORD record: ord-cfd5ecabf56a4b27a4b5f50465876b31
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018214B2

Reaction notes

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