Dimethylformamide → 3-Methylcarboxy-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepine

HRID 628003Notes

Reaction equation

HRID 628003 reaction equation
CO[C:3](=O)[C:4]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][C:13]2[CH:17]=[CH:16][S:15][CH:14]=2)[C:7](I)=[N:6][CH:5]=1.CN(C)C=O.[C:25](=O)([O-:27])[O-:26].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:3][C:4]1[C:5]([C:25]([OH:27])=[O:26])=[N:6][C:7]2[C:14]3[S:15][CH:16]=[CH:17][C:13]=3[CH2:12][CH2:11][O:10][C:8]=2[CH:9]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 57900415Methyl 6-iodo-5-(2-(thiophen-3-yl)ethoxy)nicotinate

Product 1

HCID 668693003-Methylcarboxy-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepineYield 52.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 6-Iodo-5-(2-thiophen-3-yl-ethoxy)-nicotinic acid methyl ester (4.40 g, 11.3 mmol) in N,N-Dimethylformamide (176 mL, 2270 mmol) was added potassium carbonate (9.37 g, 67.8 mmol), triphenylphosphine (1.19 g, 4.52 mmol) and palladium acetate (508 mg, 2.26 mmol). The reaction mixture was stirred at 90° C. 8 h. The reaction mixture was diluted with MeOH then filtered through celite. The filtrate was concentrated. The crude product was purified by flash chromatography EtOAc/Hex (0-100%) (product eluted at 30%) to give 3-methylcarboxy-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepine (52.8%). MS: (ESI+) 262.0

Workup

  1. custom8 h
  2. filtrationthen filtered through celite
  3. concentrationThe filtrate was concentrated
  4. customThe crude product was purified by flash chromatography EtOAc/Hex (0-100%) (product eluted at 30%)

Sources & evidence

ORD record
ord-f67f708bc7094f0bbb33c86a7e42f08e
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Reaction notes

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