Phenyl formate → phenyl 2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-4-carboxylate

HRID 715289

Reaction equation

HRID 715289 reaction equation
Cl[C:2]1[C:7]2[CH2:8][N:9]([CH:12]([C:14]3[CH:15]=[N:16][C:17]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[C:18]([CH3:20])[CH:19]=3)[CH3:13])[C:10](=[O:11])[C:6]=2[CH:5]=[CH:4][N:3]=1.[CH:27]([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:28].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>CC#N.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:20][C:18]1[CH:19]=[C:14]([CH:12]([N:9]2[C:10](=[O:11])[C:6]3[CH:5]=[CH:4][N:3]=[C:2]([C:27]([O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:28])[C:7]=3[CH2:8]2)[CH3:13])[CH:15]=[N:16][C:17]=1[O:21][CH2:22][C:23]([F:26])([F:25])[F:24]

Participants

7

Reactant 3

HCID 74626Phenyl formateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89874936HCID 89874936, compound

Product 1

HCID 89875412phenyl 2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-4-carboxylateYield 74%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-chloro-2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one (50 mg, 0.13 mmol, Intermediate-2, single enantiomer), phenyl formate (32 mg, 0.26 mmol, single enantiomer), palladium acetate (II) (0.87 mg, 0.039 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (9.0 mg, 0.016 mmol) in MeCN (1.0 mL) is heated at 80° C. overnight (T. Ueda et al, Org. Lett., 2012, 14, 3100-3103). The mixture is diluted with water, and extracted with EtOAc. The organic layer is dried over sodium sulfate and filtered. The filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (2:1 to 1:2) to give 45 mg (74% yield) of the title compound as off white solid.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer is dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate is concentrated under reduced pressure
  5. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (2:1 to 1:2)

Sources & evidence

ORD record
ord-2fa01ba4be244a6d8e19739897ba2aef
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Linked notes

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