Dimethylformamide → HCID 67210502, compound

HRID 452205Notes

Reaction equation

HRID 452205 reaction equation
[C:1]1([C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][O:3]1)=[O:2].[Br:11][C:12]1[CH:13]=[C:14]([OH:18])[CH:15]=[CH:16][CH:17]=1.CO.C[O-].[Na+].CN(C=O)C>C1(C)C(C)=CC=CC=1.C1(C)C=CC=CC=1.O>[Br:11][C:12]1[CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=1)[O:18][CH2:4][C:5]1[N:6]=[CH:7][CH:8]=[CH:9][C:10]=1[C:1]([OH:3])=[O:2]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 115633-BromophenolHCID 819439furo(3,4-b)pyridin-5(7H)-oneHCID 23694274Sodium methanolate methanol

Product 1

HCID 67210502HCID 67210502, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 7237O-XyleneSolvent

Conditions

Temperature
140 °C

Procedure

[step 1] 4-Azaphthalide (15.0 g, 111.0 mmol) and 3-bromophenol (21.0 g, 121.4 mmol) were suspended in xylene (450 mL), and 28% sodium methoxide methanol solution (31.5 mL, 166.5 mmol) was added dropwise at 140° C. After stirring at 140° C. for 1 hr, DMF (10 mL) was added and the mixture was further stirred for 3 hr. Water and toluene were added to the reaction mixture, and the mixture was partitioned. The aqueous layer was neutralized with hydrochloric acid and the precipitated solid was collected by filtration to give 2-(3-bromophenoxymethyl)nicotinic acid (16.75 g, 49%). [step 2] 2-(3-Bromophenoxymethyl)nicotinic acid (10.0 g, 32.5 mmol) obtained in step 1 and polyphosphoric acid (70 g) were stirred at 170° C. for 3 hr. The reaction mixture was added to ice, and the mixture was neutralized with aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform) to give 8-bromo-5-oxo-5,11-dihydrobenzooxepino[3,4-b]pyridine (2.52 g, 27%). [step 3] Using 8-bromo-5-oxo-5,11-dihydrobenzooxepino[3,4-b]pyridine (3.70 g, 12.8 mmol) obtained in step 2 and in the same manner as in Reference Example B10, step 2, (Z)-2-(8-hydroxymethyl-5,11-dihydrobenzooxepino[3,4-b]pyridin-5-ylidene)propiononitrile (0.086 g, 2%) and (E)-2-(8-hydroxymethyl-5,11-dihydrobenzooxepino[3,4-b]pyridin-5-ylidene)propiononitrile (0.224 g, 6%) were obtained. [step 4] Using (Z)-2-(8-hydroxymethyl-5,11-dihydrobenzooxepino[3,4-b]pyridin-5-ylidene)propiononitrile (0.084 g, 0.30 mmol) obtained in step 3 and in the same manner as in Reference Example B2, the title compound (0.056 g, 63%) was obtained.

Workup

  1. stirringthe mixture was further stirred for 3 hr
  2. customthe mixture was partitioned
  3. filtrationthe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-3beaf46167164fdea417cd446adb7765
Source dataset
uspto-grants-2013_07
Patent number
US08486980B2

Reaction notes

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