Dimethylformamide → HCID 21905451, compound

HRID 1247308Notes

Reaction equation

HRID 1247308 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[CH3:18][N:19](C)[CH:20]=[O:21].[NH2:23][CH2:24][C:25]1[CH:32]=[CH:31][C:28](C#N)=[CH:27][CH:26]=1.C1[CH2:37][O:36][CH2:35]C1>C1COCC1.CCCCCCC.C(C1C=CC=CC=1)C.CO.O1CCOCC1>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([CH:35]([O:36][CH3:37])[C:20]([NH:19][CH2:18][C:28]2[CH:31]=[CH:32][C:25]([C:24]#[N:23])=[CH:26][CH:27]=2)=[O:21])=[C:4]([F:9])[CH:3]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 826084-(Aminomethyl)benzonitrileHCID 1363131-Bromo-3,5-difluorobenzeneHCID 2724682Lithium diisopropylamide

Product 1

HCID 21905451HCID 21905451, compound

Reagents, catalysts & solvents 2

HCID 21966525Dioxane MethanolSolventHCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1-bromo-3,5-difluorobenzene (16.8 g) in THF (180 ml) was cooled to −75° C. under an argon atmosphere. A 2 M solution of lithiumdiisopropylamide in THF/heptane/ethylbenzene (43.1 ml) was slowly added at below −70° C. The mixture was stirred at −78° C. for 1 h. Dimethylformamide (12.6 ml) was added and the mixture was stirred for 2 h. The cooling bath was removed and the mixture was slowly warmed to rt. The mixture was diluted with diethyl ether and washed with 0.5 M HCl. The aqueous phase was extracted with diethyl ether. The combined organic phase was dried (MgSO4), filtered and the solvent was removed to give the crude 4-bromo-2,6-difluorobenzaldehyde (12.4 g). The crude aldehyde was reacted according to general procedure A using methanol/dioxane as a solvent. The product of this reaction was subsequently coupled with 4-aminomethyl benzonitrile according to general procedure B to give (RS)-2-(4-bromo-2,6-difluoro-phenyl)-N-(4-cyano-benzyl)-2-methoxy-acetamide. Yellow oil. MS 395.0 ([M+H]+)

Workup

  1. stirringthe mixture was stirred for 2 h
  2. customThe cooling bath was removed
  3. temperaturethe mixture was slowly warmed to rt
  4. additionThe mixture was diluted with diethyl ether
  5. washwashed with 0.5 M HCl
  6. extractionThe aqueous phase was extracted with diethyl ether
  7. dry with materialThe combined organic phase was dried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent was removed
  10. customto give the crude 4-bromo-2,6-difluorobenzaldehyde (12.4 g)

Sources & evidence

ORD record
ord-749de62ecca44fdb85085299498c7e38
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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