Acetic Acid → HCID 58360284, compound

HRID 402570Notes

Reaction equation

HRID 402570 reaction equation
C(O)(=O)C.[CH3:5][O:6][C:7]([C:9]1[N:10]=[CH:11][C:12]([CH:21]=O)=[C:13]2[CH2:18][O:17][C:16]([CH3:20])([CH3:19])[O:15][C:14]=12)=[O:8].[F:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1.C([BH3-])#N.[Na+]>CO>[F:23][C:24]1[CH:30]=[CH:29][C:27]([NH:28][CH2:21][C:12]2[CH:11]=[N:10][C:9]([C:7]([O:6][CH3:5])=[O:8])=[C:14]3[O:15][C:16]([CH3:19])([CH3:20])[O:17][CH2:18][C:13]=23)=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 97314-FluoroanilineHCID 5003444Sodium cyanoborohydrideHCID 58360280methyl 5-formyl-2,2-dimethyl-4H-[1,3]dioxino[4,5-c]pyridine-8-carboxylate

Product 1

HCID 58360284HCID 58360284, compoundYield 96.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetic acid (50 μL, 0.87 mmol) was added to a mixture of 5-Formyl-2,2-dimethyl-4H-[1,3]dioxino[4,5-c]pyridine-8-carboxylic acid methyl ester [J. Org. Chem. 1999, 64, 4537] (220 mg, 0.87 mmol) and 4-fluoroaniline (125 μL, 1.3 mmol) in dry methanol (4 mL) and stirred at room temperature for 15 min. and sodium cyanoborohydride (72 mg, 1.3 mmol) was added. This mixture was stirred at room temperature for 3 h followed by evaporation of 90% of the methanol volume under reduced pressure. The residue was extracted with dichloromethane (3×25 mL) and the combined organic layers were dried (anh. Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by silica gel (methanol/dichloromethane, 0 to 10% methanol) to give 0.290 g of methyl 5-((4-fluorophenylamino)methyl)-2,2-dimethyl-4H-[1,3]dioxino[4,5-c]pyridine-8-carboxylate (compound 21a) (96%) as a white solid MS-ESI m/z 347 [MI-1]+.

Workup

  1. stirringThis mixture was stirred at room temperature for 3 h
  2. customfollowed by evaporation of 90% of the methanol volume under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (3×25 mL)
  4. dry with materialthe combined organic layers were dried (anh. Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by silica gel (methanol/dichloromethane, 0 to 10% methanol)

Sources & evidence

ORD record
ord-616e42faea6749c2ba1b68b1d3431c79
Source dataset
uspto-grants-2014_06
Patent number
US08742123B2

Reaction notes

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