Dimethylformamide → 2-(Difluoromethyl)-4-(2-morpholinoethoxy)benzaldehyde

HRID 85169Notes

Reaction equation

HRID 85169 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:4][C:3]=1[CH:17]([F:19])[F:18].[Li]CCCC.CN([CH:28]=[O:29])C.[NH4+].[Cl-]>C1COCC1>[F:18][CH:17]([F:19])[C:3]1[CH:4]=[C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:15]=[CH:16][C:2]=1[CH:28]=[O:29]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 58208458HCID 58208458, compoundHCID 178418339Butyllithium

Product 1

HCID 838546272-(Difluoromethyl)-4-(2-morpholinoethoxy)benzaldehydeYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(2-(4-bromo-3-(difluoromethyl)phenoxy)ethyl)morpholine (123; 2.8 g, 8.38 mmol) in THF (90 mL) was added n-BuLi (1.6 M solution in hexanes, 7 mL, 11.2 mmol) at −78° C. The resulting reaction mixture was stirred at the same temperature for 1 h and DMF (1.24 g, 17 mmol) was added dropwise. After stirring the mixture at −78° C. for an additional 30 min, saturated aqueous NH4Cl was added and the mixture was extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography afforded 2-(difluoromethyl)-4-(2-morpholinoethoxy)benzaldehyde 124 (1.6 g, 67%) as a brown yellow oil.

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter stirring the mixture at −78° C. for an additional 30 min
  3. extractionthe mixture was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customPurification by chromatography

Sources & evidence

ORD record
ord-26d09b9c82ee44e4ab75a7ca36c3da36
Source dataset
uspto-grants-2014_09
Patent number
US08846947B2

Reaction notes

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